Total pelvic exenteration for locally advanced and locally recurrent rectal cancer in the elderly

Background

Total pelvic exenteration (TPE) is a radical approach for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) in case of tumour invasion into the urogenitary tract. The aim of this study is to assess surgical and oncological outcomes of TPE for LARC and LRRC in elderly patients compared to younger patients.

Indications for neoadjuvant treatment based on risk factors for poor prognosis before and after neoadjuvant chemotherapy alone in patients with locally advanced rectal cancer

IntroductionThe oncological benefit of neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to clarify the clinical risk factors for poor prognosis before and after NAC for decision making regarding additional treatment in patients with LARC.Materials and methodsWe examined a total of 96 patients with MRI-defined poor-risk locally advanced mid-low rectal cancer treated by NAC alone between 2006 and 2018. Survival outcomes and clinical risk factors for poor prognosis before and after NAC were analyzed.ResultsIn the median follow-up duration after surgery of 60 months (3–120), the rates of 5-year overall survival (OS), relapse-free survival (RFS), and local recurrence (LR) were 83.6%, 78.4%, and 8.2%, respectively. In the multivariate analyses, patients with cT4 disease had a significantly higher risk of poor OS (HR; 6.10, 95% CI; 1.32–28.15, P = 0.021) than those with cT3 disease. After NAC, ycN+ was significantly associated with a higher risk of poor OS (HR; 5.92, 95% CI; 1.27–27.62, P = 0.024) and RFS (HR; 2.55, 95% CI; 1.01–6.48, P = 0.048) than ycN-. In addition, patients with CEA after NAC (post-CEA) ≥ 5 ng/ml had a significantly higher risk LR (HR; 5.63, 95% CI; 1.06–29.93, P = 0.043).ConclusionNAC alone had an insufficient survival effect on patients with cT4 disease, ycN+, or an elevated post-CEA level. In contrast, NAC alone is a potential treatment for other patients with LARC.     

Abdominosacral resection: Long-term outcome in 86 patients with locally advanced or locally recurrent rectal cancer

Aims

The purpose of this study is to evaluate the outcome of abdominosacral resections (ASR) in patients with locally advanced or recurrent rectal cancer.

Methods

From 1994 until 2012 patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) underwent a curative ASR and were enrolled in a database. The postoperative complication rates, predictive factors on oncological outcome and survival rates were registered.

Results

Seventy-two patients with LRRC (mean age 63; 44 male, 28 female) and 14 patients with LARC (mean age 65; 6 male, 8 female) underwent ASR. R0 resection was achieved in 37 patients with LRRC and 11 patients with LARC. Twenty-seven patients underwent an R1 resection (3 in the LARC group). Eight patients had an R2 resection, compared to no patients in the LARC group. In respectively 26 and 1 patients of the LRRC and LARC groups a grade 3 or 4 complication occurred and the 30-days mortality rate was respectively 3% and 7%. The 5-years overall survival was 28% and 24% respectively.

Conclusion

En bloc radical resection remains the primary goal in the treatment of dorsally located (recurrent) rectal cancer. After thorough patient selection, ASR is a safe procedure to perform, shows acceptable morbidity rates and leads to a good oncological outcome.     

Updated systematic review of the approach to pelvic exenteration for locally advanced primary rectal cancer

ObjectivesTo review the evidence regarding surgical advances in the management of primary locally advanced rectal cancer.BackgroundThe management of rectal cancer has evolved significantly in recent decades, with improved (neo)adjuvant treatment strategies and enhanced perioperative protocols. Centralization of care for complex, advanced cases has enabled surgeons in these units to undertake more ambitious surgical procedures.MethodsA Pubmed, Ovid, Embase and Cochrane database search was conducted according to the predetermined search strategy. The review protocol was prospectively registered with PROSPERO (CRD42021245582).Results14 studies were identified which reported on the outcomes of 3,188 patients who underwent pelvic exenteration (PE) for primary rectal cancer. 50% of patients had neoadjuvant radiotherapy. 24.2% underwent flap reconstruction, 9.4% required a bony resection and 34 patients underwent a major vascular excision. 73.9% achieved R0 resection, with 33.1% experiencing a major complication. Median length of hospital stay ranged from 13 to 19 days. 1.6% of patients died within 30 days of their operation. Five-year overall survival (OS) rates ranged 29%–78%.LimitationsThe studies included in our review were mostly single-centre observational studies published prior to the introduction of modern neoadjuvant treatment regimens. It was not possible to perform a meta-analysis on the basis that most were non-randomized, non-comparative studies.ConclusionsPelvic exenteration offers patients with locally advanced rectal cancer the chance of long-term survival with acceptable levels of morbidity. Increased experience facilitates more radical procedures, with the introduction of new platforms and/or reconstructive options.     

Nucleic acid-based markers of response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

The progress that has been made in the treatment of rectal cancer has mostly resulted from multimodality strategy approach that combines surgery, chemotherapy and radiotherapy. In locally advanced rectal cancer (LARC), surgery remains the primary treatment, while neoadjuvant chemoradiotherapy (nCRT) is used to downsize or downstage the tumor before surgical resection. Highly variable response to nCRT observed in LARC patients raises the need for biomarkers to enable prediction and evaluation of treatment response in a more efficient and timely manner than currently available tools. The search for predictive biomarkers continues beyond blood proteins, which have failed in subsequent validation studies. This review presents nucleic acids-based markers and their predictive potential in LARC patients. Most of the candidate biomarkers come from relatively small single-institution studies. The only candidate biomarker that emerged as relevant in more than a single study was elevated levels of Fusobacterium nucleatum nucleic acids in tumor tissue. Considering that this marker is easily accessible through non-invasive analysis of faecal samples, its predictive potential is worth further validation. The other candidate nucleic acid-based biomarkers require more consistent studies on larger cohorts before they can be considered for use in clinical setting.     

Prognostic factors after preoperative irradiation and surgery for locally advanced rectal cancer

Aims

The experience of preoperative irradiation in clinically locally advanced rectal cancer for the period 1991–2003 is reported. Prognostic factors for survival and recurrence, and parameters for obtaining a free circumferential margin were evaluated.

Methods

A prospective cohort study of 204 M0 patients given >45 Gy preoperatively (median age 66 years; 29% women; tumour level <16 cm from the anal verge).

Results

Multivisceral and/or pelvic wall resections were performed in 61% of the patients. R0, R1 and R2 resections were achieved in 74%, 21% and 5%. Five-year survival was 52% for all patients, 60% for R0 resections, 31% for R1 and 0% for R2. The calculated 5-year recurrence rates were 13% for R0 resections and 24% for R1 resections (p < 0.035). R-stage, N-stage, age, type of rectal resection and pelvic wall resection remained significant in Cox multivariate analysis for survival. Regarding local recurrence, the following parameters were independent: N-stage, carcinoembryonic antigen (CEA) response and pelvic wall resection. Medium high tumour level and reduced histopathological differentiation are important individual factors that seem to predict increased risk for not obtaining a R0 resection.

Conclusions

After preoperative irradiation and surgery, about 50% of the patients with locally advanced rectal cancer without overt metastases (M0) can be cured.     

Anastomotic leakage in colorectal cancer surgery

The safety of colorectal surgery for oncological disease is steadily improving, but anastomotic leakage is still the most feared and devastating complication from both a surgical and oncological point of view. Anastomotic leakage affects the outcome of the surgery, increases the times and costs of hospitalization, and worsens the prognosis in terms of short- and long-term outcomes. Anastomotic leakage has a wide range of clinical features ranging from radiological only finding to peritonitis and sepsis with multi-organ failure. C-reactive protein and procalcitonin have been identified as early predictors of anastomotic leakage starting from postoperative day 2–3, but abdominal-pelvic computed tomography scan is still the gold standard for the diagnosis. Several treatments can be adopted for anastomotic leakage. However, there is not a universally accepted flowchart for the management, which should be individualized based on patient's general condition, anastomotic defect size and location, indication for primary resection and presence of the proximal stoma. Non‐operative management is usually preferred in patients who underwent proximal faecal diversion at the initial operation. Laparoscopy can be attempted after minimal invasive surgery and can reduce surgical stress in patients allowing a definitive treatment. Reoperation for sepsis control is rarely necessary in those patients who already have a diverting stoma at the time of the leak, especially in extraperitoneal anastomoses. In patients without a stoma who do not require abdominal reoperation for a contained pelvic leak, there are several treatment options, including laparoscopic diverting ileostomy combined with trans-anal anastomotic tube drainage, percutaneous drainage or recently developed endoscopic procedures, such as stent or clip placement or endoluminal vacuum‐assisted therapy. We describe the current approaches to treat this complication, as well as the clinical tests necessary to diagnose and provide an effective therapy.     

Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

BACKGROUNDFor locally advanced rectal cancer (LARC), standard therapy [consisting of neoadjuvant chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ChT)] achieves excellent local control. Unfortunately, survival is still poor due to distant metastases, which remains the leading cause of death among these patients. In recent years, the concept of total neoadjuvant treatment (TNT) has been developed, whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIMTo compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODSIn a retrospective study, we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT. High-risk for failure was defined according to the presence of at least one of the following factors: T4 stage; N2 stage; positive mesorectal fascia; extramural vascular invasion; positive lateral lymph node. TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin, CRT with capecitabine, and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid, fluorouracil and oxaliplatin prior to surgery. The primary endpoint was pathological complete response (pCR). In total, 72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTSCompared to standard therapy, TNT showed a higher proportion of pCR (23% vs 7%; P = 0.01), a lower neoadjuvant rectal score (median: 8.43 vs 14.98; P < 0.05), higher T-and N-downstaging (70% and 94% vs 51% and 86%), equivalent R0 resection (95% vs 93%), shorter time to stoma closure (mean: 20 vs 33 wk; P < 0.05), higher compliance during systemic ChT (completed all cycles 87% vs 76%; P < 0.05), lower proportion of acute toxicity grade ≥ 3 during ChT (3% vs 14%, P < 0.05), and equivalent acute toxicity and compliance during CRT and in the postoperative period. The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetric-modulated arc radiotherapy than with 3D conformal radiotherapy (32% vs 9%; P < 0.05).CONCLUSIONCompared to standard therapy, TNT provides better outcome for LARC patients with high-risk factors for failure, in terms of pCR and neoadjuvant rectal score.     

The evolving treatment paradigm of locally advanced rectal cancer: a narrative review

Background and ObjectiveSurgery is still considered the mainstay of treatment of locally advanced rectal cancer (LARC). Nevertheless, “curable” disease may still pose a great risk for both local and distant relapses. Since the early eighties of the past century, we have witnessed mounting evidence supporting the multi-modality approach to tackle this disease effectively. The multi-modality approach is variable between different positive trials. In this review, we discuss the treatment evolution of LARC, highlighting the key differences between the different contemporary strategies utilized. Based on current evidence, we sought to define distinct patient subgroups and to propose a treatment algorithm that best fits patient’s risk.MethodsWe conducted a literature search through PubMed and Google scholar. Eligible papers were phase 2/3 trials [in organ preservation (OP), observational and retrospective studies were also acceptable] published in English. We used keywords such as “locally advanced rectal cancer”, “perioperative therapy in rectal cancer”, “short course radiotherapy”, “chemoradiation in rectal cancer”, “interval to surgery”, “Neoadjuvant therapy”, “Organ preservation” and “Total neoadjuvant treatment [TNT]”.Key Content and FindingsVarious trials consistently demonstrated the benefit of preoperative radiotherapy in LARC, the role of adjuvant chemotherapy is controversial based on published studies, TNT was associated with a risk reduction in distant metastasis, and more reassuring evidence is accumulating regarding OP.ConclusionsThe treatment landscape of LARC is rapidly changing. Clinicians should carefully tailor treatment strategy based on patient’s risk.     

低位直肠癌保肛术后吻合口漏的原因及防治

目的探讨低位直肠癌保肛术后吻合口漏的原因、预防及处理方法。方法对低位直肠癌全系膜切除低位吻合手术后吻合口漏的发生及治疗情况进行回顾性分析。对吻合口漏的患者采用保守治疗（经腹部引流冲洗和会阴引流管引流）及手术治疗。结果术后发生吻合口漏18例。采用保守治疗16例,行手术治疗2例,均痊愈出院。结论低位直肠癌保肛术后吻合口漏应以预防为主,满意的术前准备,掌握低位直肠癌保肛术要点并注重操作细节是预防吻合口漏的关键。恰当引流管放置以利于充分引流对吻合口漏的治愈具有重要意义。     

Anastomotic leakage after anterior resection in patients with rectal cancer previously irradiated for prostate cancer

IntroductionThere are little data on the post-operative outcome of anterior resection (AR) for rectal cancer in men who had received radiotherapy for prostate cancer previously. The aim of this study was to assess the rate of anastomotic leakage (AL) after AR in these patients.MethodsAll men who underwent bowel resection because of rectal cancer between 2000 and 2016 and had been diagnosed previously with prostate cancer were identified by linking the Swedish Colorectal Cancer Registry with the National Prostate Cancer Register. The medical records of men who underwent AR and had previously received radiotherapy for prostate cancer were reviewed.ResultsIn total, 13299 men had undergone a bowel resection for rectal cancer, 188 of whom had previously received radiotherapy for prostate cancer. Among those who had received radiation therapy, 59 men (31%) had an AR: 50 men (85%) received a diverting ileostomy, 42 men (71%) had an American Society of Anesthesiologists score of 1–2 and 36 men (61%) had tumour stage 1–2. AL was found in 12/59 men (20%), one of whom had a re-laparotomy. There was no 90-day mortality.ConclusionsIn the combined national population-based registries, a minority of patients with rectal cancer had an AR after previous radiotherapy for prostate cancer. These patients were healthy with early cancer stages and, in this selected group of patients, the AL rate was much lower than that reported previously.     

Patterns of local recurrence in locally advanced rectal cancer after intra-operative radiotherapy containing multimodality treatment

Background and purpose

The purpose of this study is to analyze the patterns of local recurrence (LR) after intra-operative radiotherapy (IORT) containing multimodality treatment of locally advanced rectal carcinoma (LARC).

Methods and materials

Two hundred and ninety patients with LARC who underwent multimodality treatment between 1994 and 2006 were studied. For patients who developed LR, the subsite was classified into presacral, postero-lateral, lateral, anterior, anastomotic or perineal. Patient and treatment characteristics were related to subsite of LR.

Results

After 5 years, 34 patients (13.2%) developed LR. The most prominent subsite of LR was the presacral subsite. 47% of the local recurrences occurred outside the IORT field. Most recurrences developed when IORT was given dorsally, while least occurred when IORT was given ventrally. Especially after dorsal IORT a high amount of infield recurrences were observed (6 of 8; 75%). In multi-variate analysis tumor distance of more than 5 cm from the anal verge and a positive circumferential margin were associated with presacral local recurrence.

Conclusions

Multimodality treatment is effective in the prevention of local recurrence in LARC. IORT application to the area most at risk is feasible and seems effective in the prevention of local recurrence. Dorsal tumor location results in unfavourable oncologic results.     

New standard in locally advanced rectal cancer

In the following review we intend to ascertain the optimal neoadjuvant therapy in patients with locally advanced rectal cancer. In 2004, a study revealed that chemoradiotherapy (CRT) resulted in better local control when performed preoperatively rather than postoperatively, thus neoadjuvant treatment was established as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant difference between concomitant CRT over 5 wk vs short-course radiotherapy (RT). Therefore, both were established as standard neoadjuvant treatments. Later, the Stockholm III study demonstrated that short-course RT had a higher complete pathological response than long-course RT. It also showed that a delay between RT and surgery presented fewer complications. This opened a window of time to provide an early and effective systemic treatment to prevent distant metastases. Studies show that short-course RT plus oxaliplatin-based chemotherapy could achieve this. When comparing this total neoadjuvant treatment (TNT) vs concomitant CRT, the former showed greater complete pathological response and lower acute toxicity. Studies presented during 2020 have also shown the benefits of TNT in terms of complete pathological response, as well as disease and metastasis-free survival. Our review suggests that probably TNT should be the new standard treatment for these patients. However, we will have to wait for the full text publications of these studies to confirm this statement.     

Metastases in locally advanced rectal cancer undergoing curatively intended treatment

BackgroundThe main cause of mortality in locally advanced rectal cancer (LARC) is metastatic progression. The aim of the present study was to describe frequency, pattern and outcome of metastatic disease in a cohort of LARC patients after curative resection.MethodsThis was a single-centre cohort study of 628 LARC cases after neoadjuvant chemoradiotherapy/radiotherapy (CRT/RT) and surgery. Data, including the first site of metastasis, was registered in an institutional database linked to the National Cancer Registry.ResultsMetastases were diagnosed in 270 patients (43.0%) with liver and lungs as the first site in 113 and 96 cases, respectively. Involved resection margins, high tumour stage and poor response to CRT/RT were associated with metastasis development and inferior overall survival (OS). Metastasectomy was performed in 76 (67.3%) patients with liver metastases and 28 (29.2%) patients with lung metastases. Five-year OS was 89% in patients without metastases and 32% in metastatic cases. In patients selected for metastasectomy, 5-year OS was 69% and 53% for lung and liver metastases, respectively. Corresponding numbers without metastasectomy were 12% and 0%.ConclusionIn this large LARC cohort undergoing curatively intended treatment, liver and lung metastases occurred at similar frequencies. Liver as the first metastatic site was associated with inferior long-term outcome, while selection for metastasectomy was associated with better OS, with more than half of the resected patients being alive five years after LARC surgery. Our results show that the presence of resectable metastatic disease at diagnosis should not exclude a curative therapeutic approach in LARC.     

Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer

Introduction

Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands.

Upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer with synchronous liver metastases

BackgroundThe optimal treatment of locally advanced rectal cancer with synchronous liver metastases remains controversial. In this study, we aimed to evaluate the safety, efficacy, and oncologic outcomes of upfront chemotherapy and short-course radiotherapy with delayed surgery in patients with locally advanced rectal cancer and synchronous liver metastases.MethodsForty-four patients who underwent upfront chemotherapy and short-course radiotherapy with delayed surgery for locally advanced rectal cancer (cT3/4, <2.0 mm from the mesorectal fascia) with synchronous liver metastases between January 2010 and June 2017 were reviewed retrospectively. Primary and metastatic liver lesions were resected with curative intent. Upfront chemotherapy and short-course radiotherapy were administered. Thereafter, restaging, surgery only, or additional chemotherapy followed by surgery was performed.ResultsAt the time of initial diagnosis, 20 patients had <3 liver metastases; 24 patients had ≥3 liver metastases. Twenty-three patients had hemi-liver metastases; 21 patients had bilobar liver metastases. R0 resection of rectal lesions was achieved in 43 patients. Synchronous R0 resection of liver metastases was achieved in 41 patients. Postoperative complications (Clavien–Dindo Grade ≥ III) were noted in 5 patients. Grade 3/4 adverse events were observed in 26 patients. All adverse events were managed effectively with medication and supportive care. The 3-year overall survival and progression-free survival rates were 65.3% and 26.9%, respectively.ConclusionUpfront chemotherapy and short-course radiotherapy with delayed surgery appear to be safe and effective in patients with locally advanced rectal cancer and synchronous liver metastases without substantially increasing treatment induced morbidity.     

同期放化疗治疗局部晚期不可手术的直肠癌近期疗效观察

目的：观察同期放化疗治疗局部晚期不可手术的直肠癌患者的近期疗效及耐受性。方法：３８例经病理证实的局部晚期或局部 区域复发的直肠癌患者接受全盆腔三维适形放疗ＤＴ４６～５０Ｇｙ／２３～２５ｆ,后缩野至肿瘤区继续推量至ＤＴ６４～６６Ｇｙ／３２～３３ｆ,同期接受奥沙利铂１３０ｍｇ／ｍ^２ｄ_１,氟尿嘧啶３５０ｍｇ／ｍ^２ｄ_１～ｄ_５,甲酰四氢叶酸２００ｍｇ／ｍ^２ｄ_１～ｄ_５,４周为１周期,共２个周期。结果：获ＣＲ７例（１９.４％）,ＰＲ１６例（４４.４％）,ＳＤ６例（１６.７％）,ＰＤ７例（１９.４％）,总有效率（ＣＲ＋ＰＲ）为６３.９％;疼痛症状缓解率为１００％;全身状况好转率７２.２％;中位生存时间为２２个月,１年和２年总生存率分别为６７.７％和２１.３％。治疗相关的毒副反应以中性粒细胞减少、腹泻、恶心呕吐以及周围神经毒性反应为主,其３级毒副反应的发生率分别为１９.４％、１６.７％、１３.９％和１１.１％,均无３级以上毒副反应发生。结论：以奥沙利铂为基础的化疗同期联合放疗对局部晚期不可手术直肠癌患者具有较好的姑息治疗作用,其治疗依从性高,治疗相关毒性可以接受,值得临床进一步推广。     

Evaluation of the efficacy of modified De Gramont and modified FOLFOX4 regimens for adjuvant therapy of locally advanced rectal cancer

Objective: To evaluate the efficacy of modified De Gramont (mDG) and FOLFOX4 (mFOLFOX4) regimens in patients with locally advanced rectal cancer (LARC). Methods: Patients that received adjuvant chemotherapy (CT) for the treatment of LARC (stage II and III) were retrospectively evaluated. Results: A total of 231 patients were examined. Median age was 58 (range, 18-83) and, of these patients, 36 (15.6%) had stage II and 195 (84.4%) had stage III disease. While the patients with stage II disease received only mDG regimen (36, 100.0%), of the patients with stage III disease, 71 (36.5%) received mDG and 124 (63.5%) received mFOLFOX4 regimen. Patients with stage III disease showed recurrences more often, but this difference was not statistically significant. Similarly, for the patients with stage III disease, there was no statistically significant relation between the adjuvant CT regimen received and the rate of recurrence. In patients with stage II disease, who received mDG, median DFS was 101 months and median OS was 106 months. For the patients with stage III disease, the patients that received mDG showed a median DFS of 78 months and a median OS of 96 months, while the patients that received mFOLFOX4 had a median DFS of 51 months and a median OS of 78 months. Although, for the patients with stage III disease, there are major differences between the two different regimens of CT in terms of DFS and OS, this difference was not statistically significant.When the results were evaluated from the perspective of toxicity, the patients that received mFOLFOX4 showed more toxicity. Neurotoxicity, which was seen in the patients that were given mFOLFOX4, was the most prominent toxicity. Conclusions: mDG and mFOLFOX4 regimens are applicable regimens as adjuvant CT for the treatment of LARC.     

腹腔镜下直肠根治术后吻合口瘘外科操作预防及处理

术后吻合口瘘是腹腔镜下直肠癌手术最严重的并发症之一,现在笔者就所阅读的文献和临床经验总结如何从外科操作等方面预防和处理吻合口瘘。