Local excision and treatment of early node-negative anal squamous cell carcinomas in a highly HIV prevalent population.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is an uncommon cancer associated with human immunodeficiency virus (HIV) infection. There has been increasing interest in providing organ-sparing treatment in small node-negative ASCC's, however, there is a paucity of evidence about the use of local excision alone in people living with HIV (PLWH). The aim of this study was to evaluate the efficacy of local excision alone in this patient population. METHODS: We present a case series of stage 1 and stage 2 ASCC in PLWH and HIV negative patients. Data were extracted from a 20-year retrospective cohort study analysing the treatment and outcomes of patients with primary ASCC in a cohort with a high prevalence of HIV. RESULTS: Ninety-four patients were included in the analysis. Fifty-seven (61%) were PLWH. Thirty-five (37%) patients received local excision alone as treatment for ASCC, they were more likely to be younger (p = 0.037, ANOVA) and have either foci of malignancy or well-differentiated tumours on histology (p = 0.002, Fisher's exact test). There was no statistically significant difference in 5-year disease-free survival and recurrence between treatment groups, however, patients who had local excision alone and PLWH were both more likely to recur later compared to patients who received other treatments for ASCC. (72.3 months vs 27.3 months, p = 0.06, ANOVA, and 72.3 months vs 31.8 months, p = 0.035, ANOVA, respectively). CONCLUSIONS: We recommend that local excision be considered the sole treatment for stage 1 node-negative tumours that have clear margins and advantageous histology regardless of HIV status. However, PLWH who have local excision alone must have access to an expert long-term surveillance programme after treatment to identify late recurrences.

A systematic review of colorectal multidisciplinary team meetings: an international comparison.

BACKGROUND: Colorectal multidisciplinary teams (CR MDTs) were introduced to enhance the cancer care pathway and allow for early investigation and treatment of cancer. However, there are no 'gold standards' set for this process. The aim of this study was to review the literature systematically and provide a qualitative analysis on the principles, organization, structure and output of CR MDTs internationally. METHODS: Literature on the role of CR MDTs published between January 1999 and March 2020 in the UK, USA and continental Europe was evaluated. Historical background, structure, core members, education, frequency, patient-selection criteria, quality assurance, clinical output and outcomes were extracted from data from the UK, USA and continental Europe. RESULTS: Forty-eight studies were identified that specifically met the inclusion criteria. The majority of hospitals held CR MDTs at least fortnightly in the UK and Europe by 2002 and 2005 respectively. In the USA, monthly MDTs became a mandatory element of cancer programmes by 2013. In the UK, USA and in several European countries, the lead of the MDT meeting is a surgeon and core members include the oncologist, specialist nurse, histopathologist, radiologist and gastroenterologist. There were differences observed in patient-selection criteria, in the use of information technology, MDT databases and quality assurance internationally. CONCLUSION: CR MDTs are essential in improving the patient care pathway and should express clear recommendations for each patient. However, a form of quality assurance should be implemented across all MDTs.

Systematic review of classification systems for locally recurrent rectal cancer.

BACKGROUND: Classification of pelvic local recurrence (LR) after surgery for primary rectal cancer is not currently standardized and optimal imaging is required to categorize anatomical site and plan treatment in patients with LR. The aim of this review was to evaluate the systems used to classify locally recurrent rectal cancer (LRRC) and the relevant published outcomes. METHODS: A systematic review of the literature prior to April 2020 was performed through electronic searches of the Science Citation Index Expanded, EMBASE, MEDLINE and CENTRAL databases. The primary outcome was to review the classifications currently in use; the secondary outcome was the extraction of relevant information provided by these classification systems including prognosis, anatomy and prediction of R0 after surgery. RESULTS: A total of 21 out of 58 eligible studies, classifying LR in 2086 patients, were reviewed. Studies used at least one of the following eight classification systems proposed by institutions or institutional groups (Mayo Clinic, Memorial Sloan-Kettering - original and modified, Royal Marsden and Leeds) or authors (Yamada, Hruby and Kusters). Negative survival outcomes were associated with increased pelvic fixity, associated symptoms of LR, lateral compared with central LR and involvement of three or more pelvic compartments. A total of seven studies used MRI with specifically defined anatomical compartments to classify LR. CONCLUSION: This review highlights the various imaging systems in use to classify LRRC and some of the prognostic indicators for survival and oncological clearance based on these systems. Implementation of an agreed classification system to document pelvic LR consistently should provide more detailed information on anatomical site of recurrence, burden of disease and standards for comparative outcome assessment.

Factors associated with metachronous metastases and survival in locally advanced and recurrent rectal cancer.

BACKGROUND: Better understanding of the impact of metachronous metastases in locally advanced and recurrent rectal cancer may improve decision-making. The aim of this study was to investigate factors influencing metachronous metastasis and its impact on survival in patients who have a beyond total mesorectal excision (bTME) operation. METHODS: This was a retrospective study of consecutive patients who had bTME surgery for locally advanced and recurrent rectal cancer at a tertiary referral centre between January 2006 and December 2016. The primary outcome was overall survival. Cox proportional hazards regression analyses were performed. The influence of metachronous metastases on survival was investigated. RESULTS: Of 220 included patients, 171 were treated for locally advanced primary tumours and 49 for recurrent rectal cancer. Some 90·0 per cent had a complete resection with negative margins. Median follow-up was 26·0 (range 1·5-119·6) months. The 5-year overall survival rate was 71·1 per cent. Local recurrence and metachronous metastasis rates were 11·8 and 22·2 per cent respectively. Patients with metachronous metastases had a worse overall survival than patients without metastases (median 52·9 months versus estimated mean 109·4 months respectively; hazard ratio (HR) 6·73, 95 per cent c.i. 3·23 to 14·00). Advancing pT category (HR 2·01, 1·35 to 2·98), pN category (HR 2·43, 1·65 to 3·59), vascular invasion (HR 2·20, 1·22 to 3·97) and increasing numbers of positive lymph nodes (HR 1·19, 1·07 to 1·16) increased the risk of metachronous metastasis. Nine of 17 patients (53 per cent) with curatively treated synchronous metastases at presentation developed metachronous metastases, compared with 40 of 203 (19·7 per cent) without synchronous metastases (P = 0·002). Corresponding median length of disease-free survival was 17·5 versus 90·8 months (P < 0·001). CONCLUSION: As metachronous metastases impact negatively on survival after bTME surgery, factors associated with metachronous metastases may serve as selection tools when determining suitability for treatment with curative intent.

ANTECEDENTES: Una mejor comprensión del impacto de las metástasis metacrónicas en el cáncer de recto localmente avanzado y recidivante puede mejorar la toma de decisiones. El objetivo de este estudio fue investigar los factores que influyen en las metástasis metacrónicas y su impacto en la supervivencia en pacientes sometidos a una operación más amplia que una escisión total del mesorrecto (beyond total mesorectal excision, bTME). MÉTODOS: Se trata de un estudio retrospectivo de pacientes consecutivos sometidos a operaciones bTME por cáncer de recto localmente avanzado y recidivante en un centro de referencia terciario entre enero 2006 y diciembre 2016. El resultado primario fue la supervivencia global. Se realizaron análisis de regresión de riesgos proporcionales de Cox. Se evaluó la influencia de las metástasis metacrónicas en la supervivencia. RESULTADOS: De un total de 220 pacientes incluidos, 171 fueron tratados por tumores primarios localmente avanzados y 49 por una recidiva de cáncer de recto. Un 90% fue sometido a una resección completa con márgenes negativos. La mediana de seguimiento fue 260 meses (rango 1,5 a 119,6 meses). La supervivencia global a los 5 años fue del 71%. Las tasas de recidiva local y metástasis metacrónicas fueron del 11,8% y del 22,2%, respectivamente. Los pacientes con metástasis metacrónicas presentaron una supervivencia peor en comparación con los pacientes sin metástasis (mediana 46,7 versus 109,4 meses, cociente de riesgos instantáneos, hazard ratio, HR 6,73, i.c. del 95% 3,23-14,00). Los factores que aumentaron el riesgo de metástasis metacrónicas fueron un estadio T patológico avanzado HR 2,01 (i.c. del 95% 1,35-2,98), estadio N HR 2,43 (i.c. del 95% 1,65-3,59), invasión vascular HR 2,20 (i.c. del 95% 1,22-3,97) y un número creciente de ganglios linfáticos positivos HR 1,19 (i.c. del 95% 1,07-1,16). En pacientes con metástasis sincrónicas tratadas con intención curativa de inicio, el 52,9% desarrollaron metástasis metacrónicas versus el 19,7% en pacientes sin metástasis sincrónicas (P = 0,002). La mediana de la supervivencia libre de enfermedad (disease-free survival, DFS) correspondiente fue de 17,5 versus 90,8 meses (P < 0,0001). CONCLUSIÓN: Dado que las metástasis metacrónicas tienen un impacto negativo en la supervivencia tras cirugía bTME, los factores asociados con las metástasis metacrónicas pueden servir como variables de selección para decidir la idoneidad de un tratamiento con intención curativa.

Postoperative chemotherapy improves survival in patients with resected high-risk Stage II colorectal cancer: results of a systematic review and meta-analysis.

AIM: The aim was to assess the benefit of adjuvant chemotherapy in high-risk Stage II colorectal cancer. METHOD: A systematic literature review and meta-analysis was performed comparing survival in patients with resected Stage II colorectal cancer and high-risk features having postoperative chemotherapy vs no chemotherapy. RESULTS: Of 1031 articles screened, 29 were included, reporting on 183 749 participants. Adjuvant chemotherapy significantly improved overall survival [hazard ratio (HR) 0.61, P < 0.0001], disease-specific survival (HR = 0.73, P = 0.05) and disease-free survival (HR = 0.59, P < 0.0001) compared to no chemotherapy. Adjuvant chemotherapy significantly increased 5-year overall survival (OR = 0.53, P = 0.0008) and 5-year disease-free survival (OR = 0.50, P = 0.001). Overall survival and disease-free survival remained significantly prolonged during subgroup analysis of studies published from 2015 onwards (HR = 0.60, P < 0.0001; HR = 0.65, P = 0.0001; respectively), in patients with two or more high-risk features (HR = 0.59, P = 0.0001; HR = 0.70, P = 0.03; respectively) and in colon cancer (HR = 0.61, P < 0.0001; HR = 0.51, P = 0.0001; respectively). Overall survival, disease-specific survival and disease-free survival during subgroup analysis of individual high-risk features were T4 tumour (HR = 0.58, P < 0.0001; HR = 0.50, P = 0.003; HR = 0.75, P = 0.05), < 12 lymph nodes harvested (HR = 0.67, P = 0.0002; HR = 0.80, P = 0.17; HR = 0.72, P = 0.02), poor differentiation (HR = 0.84, P = 0.35; HR = 0.85, P = 0.23; HR = 0.61, P = 0.41), lymphovascular or perineural invasion (HR = 0.55, P = 0.05; HR = 0.59, P = 0.11; HR = 0.76, P = 0.05) and emergency surgery (HR = 0.60, P = 0.02; HR = 0.68, P = 0.19). CONCLUSION: Adjuvant chemotherapy in high-risk Stage II colorectal cancer results in a modest survival improvement and should be considered on an individual patient basis. Due to potential heterogeneity and selection bias of the included studies, and lack of separate rectal cancer data, further large randomized trials with predefined inclusion criteria and standardized chemotherapy regimens are required.

Ex vivo specimen MRI and pathology confirm a rectosigmoid mesenteric waist at the junction of the mesorectum and mesocolon.

AIM: Continuity of the mesentery has recently been established and may provide an anatomical basis for optimal colorectal resectional surgery. Preliminary data from operative specimen measurements suggest there is a tapering in the mesentery of the distal sigmoid. A mesenteric waist in this area may be a risk factor for local recurrence of colorectal cancer. This study aimed to investigate the anatomical characteristics of the mesentery at the colorectal junction. METHOD: In this cross-sectional study, 20 patients were recruited. After planned colorectal resection, the surgical specimens were scanned in a MRI system and subsequently dissected and photographed as per national pathology guidelines. Mesenteric surface area and linear measurements were compared between MRI and pathology to establish the presence and location of a mesenteric waist. RESULTS: Specimen analysis confirmed that a narrowing in the mesenteric surface area was consistently apparent at the rectosigmoid junction. Above the anterior peritoneal reflection, the surface area and posterior distance of the mesentery of the upper rectum initially decreased before increasing as the mesentery of the sigmoid colon. These anatomical properties created the appearance of a mesenteric 'waist' at the rectosigmoid junction. Using the anterior reflection as a reference landmark, the rectosigmoid waist occurred at a mean height of 23.6 and 21.7 mm on MRI and pathology, respectively. CONCLUSION: A rectosigmoid waist occurs at the junction of the mesorectum and mesocolon, and is a mesenteric landmark for the rectum that is present on both radiology and pathology.

Expert consensus on a train-the-trainer curriculum for robotic colorectal surgery.

AIM: Robotic techniques are being increasingly used in colorectal surgery. There is, however, a lack of training opportunities and structured training programmes. Robotic surgery has specific problems and challenges for trainers and trainees. Ergonomics, specific skills and user-machine interfaces are different from those in traditional laparoscopic surgery. The aim of this study was to establish expert consensus on the requirements for a robotic train-the-trainer curriculum amongst robotic surgeons and trainers. METHOD: This is a modified Delphi-type study involving 14 experts in robotic surgery teaching. A reiterating 19-item questionnaire was sent out to the same group and agreement levels analysed. A consensus of 0.8 or higher was considered to be high-level agreement. RESULTS: Response rates were 93-100% and most items reached high levels of agreement within three rounds. Specific requirements for a robotic faculty development curriculum included maximizing dual-console teaching, theatre team training, nontechnical skills training, patient safety, user-machine interface training and telementoring. CONCLUSION: A clear need for the development of a train-the-trainer curriculum has been identified. Further research is needed to assess feasibility, effectiveness and clinical impact of a robotic train-the-trainer curriculum.

Influence of the level of sacrectomy on survival in patients with locally advanced and recurrent rectal cancer.

BACKGROUND: Exenterative surgery for locally advanced rectal cancer may involve partial sacrectomy to achieve complete resection. High sacrectomy is technically challenging, and can be associated with high morbidity and mortality rates. The aim of this study was to determine the influence of the level of sacrectomy on the survival of patients with locally advanced rectal cancer. METHODS: This was an international multicentre retrospective analysis of patients undergoing exenterative abdominosacrectomy between July 2006 and June 2016. High sacrectomy was defined as resection at or above the junction of S2-S3; low sacrectomy was below the S2-S3 junction. Kaplan-Meier survival analysis was used to assess overall survival and cancer-specific survival. Predictive factors were determined using Cox regression analysis. RESULTS: A total of 345 patients were identified, of whom 91 underwent high sacrectomy and 254 low sacrectomy. There was no difference in 5-year overall survival (53 versus 44·1 per cent; P = 0·216) or cancer-specific survival (60 versus 56·1 per cent; P = 0·526) between high and low sacrectomy. Negative margin rates were similar for primary and recurrent disease: 65 of 90 (72 per cent) versus 97 of 153 (63·4 per cent) (P = 0·143). Level of sacrectomy was not a significant predictor of mortality (P = 0·053). Positive resection margin and advancing age were the only significant predictors for death, with hazard ratios of 2·78 (P < 0·001) and 1·02 (P = 0·020) respectively. CONCLUSION: There was no survival difference between patients who underwent high or low sacrectomy. In appropriately selected patients, high sacrectomy is feasible and safe.

Suture choice to reduce occurrence of surgical site infection, hernia, wound dehiscence and sinus/fistula: a network meta-analysis.

BACKGROUND: There are many options and little guiding evidence when choosing suture types with which to close the abdominal wall fascia. This network meta-analysis investigated the effect of suture materials on surgical site infection, hernia, wound dehiscence and sinus/fistula occurrence after abdominal surgery. The aim was to provide clarity on whether previous recommendations on suture choice could be followed with confidence. METHODS AND METHODS: In February 2017, the Cochrane Central Register of Controlled Trials, Medline, EMBASE and Science Citation Index Expanded were searched for randomised controlled trials investigating the effect of suture choice on these four complications in closing the abdomen. A reference search of identified trials was performed. Prisma guidelines and the Cochrane risk of bias tool were followed in the data extraction and synthesis. Two review authors screened titles and abstracts of trials identified. A random effect model was used for the surgical site infection network based on the deviance information criterion statistics. RESULTS: Thirty-one trials were included (11,533 participants). No suture material reached the predetermined 90% probability threshold for determination of 'best treatment' for any outcome. Pairwise comparisons largely showed no differences between suture types for all outcomes measured. However, nylon demonstrated a reduction in the occurrence of incisional hernias with respect to two commonly used absorbable sutures: polyglycolic acid (odds ratio, OR 1.91; 95% confidence interval, CI, 1.01-3.63) and polyglyconate (OR 2.18; 95% CI 1.17-4.07). CONCLUSIONS: No suture type can be considered the 'best treatment' for the prevention of surgical site infection, hernia, wound dehiscence and sinus/fistula occurrence.

Comparison of guidelines for the management of rectal cancer.

A comparison between NCCN, ESMO and JSCCR Guidelines is presented, concerning the treatment of rectal cancer, with an analysis and discussion of their discrepancies. Differences indicate areas for research.

A meta-analysis assessing the survival implications of subclassifying T3 rectal tumours.

AIM: Although T3 tumour subclassifications have been linked to prognosis, its mandatory adoption in histopathological reports has not been incorporated. This article focusses on the survival outcomes in patients with T3 rectal cancer according to extramural spread beyond the muscularis propria. METHODS: A systematic review of all studies up to January 2016, without language restriction, was identified from MEDLINE, Cochrane Controlled Trials Register (1960-2016) and Embase (1991-2016). All studies reporting on survival and T3 tumours with a defined cut-off of 5 mm ± 1 mm tumour invasion beyond the muscularis propria for rectal cancers were included. Hazard ratios were extracted directly from the studies or from survival curves using the technique described by Parmar. Quality assessment was performed using the Newcastle-Ottawa scale. RESULTS: Tumours with invasion more than 5 ± 1 mm from the muscularis propria had statistically significantly worse overall survival (natural log of the hazard ratio [lnHR]: 1.40 [1.06, 2.04], p < 0.001) and there was no statistically significant heterogeneity (χ2 = 1.541, df = 3, p = 0.673, I2 = 0). There was statistically significantly worse disease-free survival in more invasive tumours (lnHR: 1.49 [1.19, 2.00], p < 0.001) and cancer specific survival (lnHR: 1.22 [0.917, 1.838], p < 0.001). Overall survival in patients who had preoperative therapy was higher in patients with less invasion beyond the muscularis propria [p < 0.01]. CONCLUSIONS: Subclassifying all T3 rectal tumours according to the depth of spread with a cut-off of 5±1 mm beyond the muscularis propria is prognostically relevant for overall survival, disease-free survival and cancer-specific survival irrespective of the nodal status; therefore, subclassifying T3 tumours should be a reporting requirement in histopathology reports.

Variation in landmarks for the rectum: an MRI study.

AIM: This study aimed to assess the reliability of measurements and bony landmarks for the rectosigmoid junction on MRI. METHOD: The staging MRI scans for 100 patients were reviewed. The junction of the mesorectum and mesocolon was used to identify the rectum and sigmoid. The performance of current metric measurements or bony landmarks was then compared against the actual anatomical bowel segment. RESULTS: The mean distance of the sigmoid take-off from the anal verge was 12.6 cm (SD 1.8 cm, range 9.4-19.0 cm). At a cutoff of 12 cm, the anatomical bowel segment was found to be sigmoid colon rather than rectum in 35% of patients. At 15 and 16 cm the bowel segment was sigmoid in 84% and 96% of patients, respectively. At the sacral promontory and the third sacral segment, the bowel segment was sigmoid in 28% and 100% of patients, respectively. CONCLUSION: Current definitions of the rectum that rely on arbitrary measurements or bony landmarks will not locate the correct point of transition between the rectum and sigmoid in the majority of patients. The sigmoid take-off offers an alternative, anatomically bespoke, landmark.

Mixed adenoneuroendocrine carcinoma of the colon and rectum.

Mixed adenoneuroendocrine carcinoma (MANEC) are rare cancers of the gastrointestinal (GI) and pancreatobiliary tract. They are characterized by the presence of a combination of epithelial and neuroendocrine elements, where each component represents at least 30% of the tumour. Review of literature and consolidation of clinicopathological data. Sixty-one cases of colorectal MANEC have been reported in literature and one seen in this centre. The median age of the patients affected was 61.9 ± 12.4 years (20-94 years). Male to female ratio is 1.0:1.2. Presentations were similar to other colorectal malignancies. 58.0% of colorectal MANECs were found in the right colon, 8.1% cases in the transverse, 16.1% in the left colon, 16.1% in the rectum. These tumours appeared invasiveness 79.1% were T3-T4. Over 90% of cases were presented with metastatic disease. The majority of patient underwent surgical resection of the primary cancer (96.6%). Of these, 10 operations (17.9%) were emergency operations due to obstruction, perforation, or bleeding. Three patients received first line palliative care. In eight cases (13.8%), patients underwent adjuvant chemotherapy. The median overall survival after diagnosis was 10 ± 2.4 months (95% CI: 5.37-14.64 months). MANECs are rare but aggressive colorectal cancers. Surgical resection of localized disease with adjuvant chemotherapy appears to significantly improve survival in small case series. Further understanding through the sharing of experiences is required.