Piotr Richter

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: A prospective multicentre study

PURPOSE To assess local control after preoperative radiation and local excision and to determine an optimal radiotherapy regimen. METHODS Eighty-nine patients with G1-2 rectal adenocarcinoma <3-4 cm; unfavourable cT1N0 (23.6%), cT2N0 (62.9%) or borderline cT2/cT3N0 (13.5%) received 5 × 5 Gy plus 4 Gy boost (71.9%) or 55.8 Gy in 31 fractions with 5-FU and leucovorin (28.1%). Local excision (traditional technique 56.2%, transanal endoscopic microsurgery 41.6%, Kraske procedure 2.2%) was performed 6-8 weeks later. If patients were downstaged to ypT0-1 without unfavourable factors (good responders), this was deemed definitive treatment. Immediate conversion to radical surgery was recommended for remaining patients. RESULTS Good response to radiation was seen in 67.2% of patients in the short-course group and in 80.0% in the chemoradiation group, p = 0.30. Local recurrence at 2 years (median follow-up) in good responders was 11.8% in the short-course group and 6.2% in the chemoradiation group, p = 0.53. In the total group, a lower rate of local recurrence at 2 years was observed in elderly patients (>69 years, median value) when compared to the younger patients; 8.3% vs. 27.7%, Cox analysis hazard ratio 0.232, p = 0.016. A total of 18 patients initially managed with local excision required conversion to abdominal surgery but either refused it or were unfit. In this group, local recurrence at 2 years was 37.1%. CONCLUSIONS This study suggests an acceptable local recurrence rate after preoperative radiotherapy and local excision of small, radiosensitive tumours in elderly patients.

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

BACKGROUND AND PURPOSE To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. MATERIALS AND METHODS Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5x5Gy+4Gy boost (N=31) or chemoradiation (50.4Gy+5.4Gy boost, 1.8Gy per fraction+5-fluorouracyl and leucovorin; N=13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. RESULTS The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. CONCLUSION Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.

Total thyroidectomy for benign thyroid disease: is it really worthwhile?

Objective:To compare the outcomes of bilateral subtotal (BST) versus total thyroidectomy (TT) for benign bilateral thyroid disease (BBTD). Background:The extent of thyroid resection in benign goiter is controversial. Potential advantages of TT over BST may include: one-stage removal of incidental thyroid cancer, and a lower risk for goiter recurrence. However, these potential advantages should outweigh the risk of morbidity. Methods:A retrospective cohort study was conducted of 8032 patients with BBTD operated in a single institution. Patients in Group A underwent BST (1999–2004, n = 5214; follow-up 72.3 ± 12.4 months), whereas patients in Group B underwent TT (2005–2009, n = 2918; follow-up 36.3 ± 10.6 months). Data were collected prospectively. The analysis included: prevalence of incidental thyroid cancer, recurrent goiter, need for completion thyroidectomy, and morbidity. Results:Incidental thyroid cancer was found in 406 (5.00%) patients. One hundred twelve (2.15%) BST versus 3 (0.10%) TT patients required completion thyroidectomy (P < 0.001). Recurrent goiter was diagnosed in 364 (6.99%) BST patients and 165 (45.33%) required reoperation versus 0% after TT (P < 0.001). The prevalence of transient and permanent hypoparathyroidism was 2.70% and 0.15% versus 13.12% and 0.10% (BST vs. TT, P < 0.001 and P = 0.65, respectively). The prevalence of temporary and permanent RLN injury was 2.30% and 0.71% versus 2.60% versus 0.69% (BST vs. TT, respectively; nonsignificant). Conclusions:Compared to TT, BST resulted in a significantly higher rate of completion thyroidectomy for incidentally diagnosed thyroid cancer and need for redo surgery for recurrent goiter. The extent of surgical resection had no significant impact on the prevalence of permanent complications. Registration number: NCT01273714 (http://www.clinicaltrials.gov).

Clinical value of intraoperative neuromonitoring of the recurrent laryngeal nerves in improving outcomes of surgery for well-differentiated thyroid cancer.

UNLABELLED The recurrent laryngeal nerve (RLN) is particularly prone to injury during thyroidectomy in case of extralaryngeal bifurcation being present in approximately one-third of patients near the inferior thyroid artery or ligament of Berry. Meticulous surgical dissection in this area may be additionally facilitated by the use of intraoperative neuromonitoring (IONM) to assure safe and complete removal of thyroid tissue. The aim of the study was to verify the hypothesis that meticulous surgical technique of tissue dissection in the area of the posterior surface of the thyroid capsule and adjacent RLN may be additionally facilitated by intraoperative neuromonitoring (IONM), and may contribute to increasing the safety and radicalness of total thyroidectomy in patients with well-differentiated thyroid cancer. MATERIAL AND METHODS The outcomes of total thyroidectomy with level VI lymph node clearance for well-differentiated thyroid cancer (WDTC; pT1-3, N0-1, Mx) were retrospectively compared between 151 patients undergoing surgery with IONM (01/2005-06/2009) and 151 patients undergoing surgery without IONM (2003-2004). RLN morbidity (calculated for nerves at risk) was assessed by videolaryngoscopy or indirect laryngoscopy (mandatory before and after surgery and at 12-month follow-up). The anatomical course of the extralaryngeal segment of RLNs were analyzed in detail in each operation. Thyroid iodine uptake (131I) was measured during endogenous TSH stimulation test a week before radioiodine therapy. RESULTS Among patients operated with vs. without IONM, the early RLN injury rate was 3% vs. 6.7% (p=0.02), including 2% vs. 5% (p=0.04) of temporary nerve lesions, and 1% vs. 1.7% of permanent nerve events (p=0.31), respectively. Extralaryngeal RLN bifurcation was identified in 42 (27.8%) vs. 25 (16.6%) of patients operated with vs. without IONM, respectively (p=0.001). Mean I-131 uptake following total thyroidectomy with vs. without IONM was 0.67 ± 0.39% vs. 1.59 ± 0.69% (p<0.001). 131I uptake lower than 1% was found in 106 (70.2%) vs. 38 (25.2%) patients operated with vs. without IONM, respectively (p<0.001). CONCLUSIONS Most patients with WDTC who undergo total thyroidectomy have a small amount of residual thyroid tissue. The use of IONM may improve the outcomes of surgery among these patients by both increasing the completeness of total thyroidectomy and significantly reducing the prevalence of temporary RLN injury. The possible mechanism of this improvement is the aid in dissection at the level of the Berrys ligament offered by IONM which enhances the surgeons ability to identify a branched RLN, and allows for reduction of traction injury and neuropraxia of the anterior branch of bifid nerves.

Anorectal and sexual functions after preoperative radiotherapy and full-thickness local excision of rectal cancer.

AIMS Local excision with preoperative radiotherapy may be considered as alternative management to abdominal surgery alone for small cT2-3N0 tumours. However, little is known about anorectal and sexual functions after local excision with preoperative radiotherapy. Evaluation of this issue was a secondary aim of our previously published prospective multicentre study. METHODS Functional evaluation was based on a questionnaire completed by 44 of 64 eligible disease-free patients treated with preoperative radiotherapy and local excision. Additionally, ex post, these results were confronted with those recorded retrospectively in the control group treated with anterior resection alone (N = 38). RESULTS In the preoperative radiotherapy and local excision group, the median number of bowel movements was two per day, incontinence of flatus occurred in 51% of patients, incontinence of loose stool in 46%, clustering of stools in 59%, and urgency in 49%; these symptoms occurred often or very often in 11%-21% of patients. Thirty-eight per cent of patients claimed that their quality of life was affected by anorectal dysfunction. Nineteen per cent of men and 20% of women claimed that the treatment negatively influenced their sexual life. The anorectal functions in the preoperative radiotherapy and local excision group were not much different from that observed in the anterior resection alone group. CONCLUSIONS Our study suggests that anorectal functions after preoperative radiotherapy and local excision may be worse than expected and not much different from that recorded after anterior resection alone. It is possible that radiotherapy compromises the functional effects achieved by local excision.

Altered plasma fibrin clot properties in patients with digestive tract cancers: Links with the increased thrombin generation ☆

OBJECTIVES Evidence indicates that cancer patients have increased thromboembolic risk. Given a potential role of prothrombotic clot phenotype in thrombosis, we investigated plasma fibrin clot properties in patients with digestive tract cancer (DTC). METHODS We studied 44 consecutive patients with DTC, including 26 subjects with colorectal cancer, versus 47 controls matched for demographics and cardiovascular risk factors. We evaluated ex vivo plasma fibrin clot permeability (Ks), turbidimetry (lag phase and maximum absorbance, ΔAbs), and efficiency of fibrinolysis using 3 different measures (CLT, t50% and maximum rate of d-dimer release from clots, d-Drate). RESULTS Patients with DTC had lower Ks (-11.5%, p=0.016), shorter lag phase (-5%, p=0.019), longer CLT (+17%, p<0.001) and t50% (+8%, p=0.031), and reduced d-Drate (-12%, p<0.001) compared with controls. After adjustment for potential confounders, thrombin-antithrombin (TAT) complexes were the independent predictor of CLT and t50% in the patients, while Ks was independently associated with tissue plasminogen activator but not with TAT. In high grade tumor patients (n=26) compared with the remainder (n=18), Ks was lower (p=0.004), and lag phase shorter (p=0.03), while CLT (p=0.012) and t50% (p=0.008) were longer, suggesting more profound unfavorable alterations in fibrin clots properties. CONCLUSIONS This study is the first to show that patients with DTC tend to form less permeable fibrin clots relatively resistant to lysis. Prothrombotic clot phenotype might represent a novel prothrombotic mechanism in cancer patients.

Evaluation of serum microRNA biomarkers for gastric cancer based on blood and tissue pools profiling: the importance of miR-21 and miR-331.

Background:High stability and disease-specific disarrangements suggest that microRNA molecules (miRNAs) present in body fluids are ideally suited for diagnostic applications, including gastric cancer (GC). However, the actual source of circulating miRNA biomarkers in GC has not been adequately evaluated, particularly in the Western populations that have some distinct characteristics compared with Asian patients.Methods:Twenty treatment-naive patients with GC along with 20 cancer-free controls were recruited. miRCURY LNA miRNA microarrays were used for miRNA expression profiling in primary tumours and adjacent healthy mucosa. Differentially expressed serum miRNAs were identified with a high throughput TaqMan OpenArray technology in tumour-draining veins of the portal system, as well as peripheral blood of the patients and controls.Results:Tissue profiling identified 108 sequences differentially expressed between primary tumours and adjacent mucosa (87 upregulated and 21 downregulated). Twenty miRNAs found in serum of GC patients showed expression levels higher than in controls. However, only seven of these molecules were overexpressed in primary tumours (miR-130a, miR-331, miR-19a, miR-223, miR-106a, miR-21, and miR-374). Moreover, expression of miR-331 and miR-21 was significantly higher in the peripheral circulation compared to tumour-draining veins of the portal system.Conclusions:The results indicate that the majority of potential serum miRNA biomarkers may originate from tissues other than the primary tumour.

Definition of the rectum and level of the peritoneal reflection – still a matter of debate?

Introduction Pathological lesions of the rectum are common and their management requires detailed knowledge of pelvic anatomy. There has been considerable debate as to the definition of the rectum and the variability of the level of the peritoneal reflection. The lack of a clear consensus was proven in the research by McCullen et al. regarding the current pattern of practice for the investigation of primary rectal cancer by general surgeons. Aim To carry out bibliographic research on the definition of the rectum and level of the peritoneal reflection. Material and methods A web-based published literature search of PubMed, Ovid Medline, Science Direct and Springer was made. Results The paper presents the current definitions of proximal and distal margin of the rectum and level of peritoneal reflection based not only on the results of tests on cadavers but also on living humans. Conclusions The results of tests on living humans allow more accurate qualification of patients for local excision, which is particularly important for patients with colorectal cancer.

Adaptation of Quality of Life Module EORTC QLQ-CR29 for Polish Patients with Rectal Cancer - Initial Assessment of Validity and Raeliability

Heath related quality of life has been an important object of interest in the clinical practice, focused on assessment of treatment effects from patients point of view, with particular emphasis placed on effect of treatment on daily patient functioning. Concept of health-related quality of life needs valid and reliable instruments.The aim of the study was to present the process of validation of a new version of EORTC QLQ-CR29 module in Polish patients suffering from rectal cancer.Material and methods. EORTC QLQ-CR29 module comprises 29 questions, and was adapted to Polish cultural conditions based on EORTC procedure. Data collected from 20 patients were analyzed, their agreement with theoretical and empirical structure was assessed. Convergent and discriminant validity were analyzed with multi trait scaling.Reliability was assessed with Cronbach alpha coefficient. Known group validity was assessed in terms of differences between men and women, and between stoma and non-stoma patients. Exact Mann-Whitney test was used. P values lower than 0.05 were considered significant.Results. Scales built on bases of empirical model of module had higher validity and reliability than those based on theoretical model.There were no significant differences between men and women in health-related quality of life. Significantly higher values were observed in non-stoma patients on body image scale and for leakage of stool item. Reversed relationship was observed in case of abdominal and buttocks pain, as well as embarrassment because of bowel movements.Conclusions. Module CR29 is a valid and reliable tool, which enables standardized measurement of treatment effects, suggested for use as main tool measuring impact of disease itself and applied treatment on health-related quality of life of rectal cancer patients.

Vulnerable Elderly Survey 13 as a screening method for frailty in Polish elderly surgical patient--prospective study.

UNLABELLED The Vulnerable Elders Survey (VES-13) is a simple function based frailty screening tool that can be also administered by the nonclinical personnel within 5 minutes and has been validated in the out- and in patient clinic and acute medical care settings. The aim of the study was to validate the accuracy of the VES-13 screening method for predicting the frailty syndrome based on a CGA in polish surgical patients. MATERIAL AND METHODS We included prospectively 106 consecutive patients ≥65, that qualify for abdominal surgery (both due to oncological and benign reasons), at the tertiary referral hospital.We evaluated the diagnostic performance of VES-13 score comparing to the results from the CGA, accepted as the gold standard for identifying at risk frail elderly patients. RESULTS The prevalence of frailty as diagnosed by CGA was 59.4%. There was significantly higher number of frail patients in the oncological group (78% vs. 31%; p<0.01). According to the frailty screening methods, the frailty prevalence was 45.3%. The VES-13 score had a 60% sensitivity and 78% specificity in detecting frailty syndrome. The positive and negative predictive value was 81% and 57%, respectively. The overall predictive capacity was intermediate (AUC=0.69) CONCLUSIONS: At present, the VES-13 screening tool for older patients cannot replace the comprehensive geriatric assessment; this is due to the insufficient discriminative power to select patients for further assessment. It might be helpful in a busy clinical practice and in facilities that do not have trained personal for geriatric assessment.