Satish K. Warrier

Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review

Pathological complete response to neoadjuvant chemoradiotherapy is found in 20% of patients with rectal cancer undergoing long‐course chemoradiotherapy. Some authors have suggested that these patients do not need to undergo surgery and can be managed with careful follow‐up, with surgery only used in the event of clinical failure. Widespread adoption of this regimen is limited by the accuracy of methods to confirm a pathological complete response (pCR).

Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A systemic review

Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (pCR) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit.

The Outcomes and Patterns of Treatment Failure After Surgery for Locally Recurrent Rectal Cancer

Objective: To assess the outcomes and patterns of treatment failure of patients who underwent pelvic exenteration surgery for recurrent rectal cancer. Background: Despite advances in the management of rectal cancer, local recurrence still occurs. For appropriately selected patients, pelvic exenteration surgery can achieve long-term disease control. Methods: Prospectively maintained databases of 5 high volume institutions for pelvic exenteration surgery were reviewed and data combined. We assessed the combined endpoints of overall 5-year survival, cancer-specific 5-year mortality, local recurrence, and the development of metastatic disease. Results: Five hundred thirty-three patients who had undergone surgery for locally recurrent rectal cancer were identified. Five-year cancer-specific survival for patients with a complete (R0) resection is 44%, which was achieved in 59% of patients. For those with R1 and R2 resections, the 5-year survival was 26% and 10%, respectively. Radical resection required sacrectomy in 170 patients (32%), and total cystectomy in 105 patients (20%). Treatment failure included local recurrence alone in 75 patients (14%) and systemic metastases with or without local recurrence in 226 patients (42%). Chemoradiotherapy before exenteration was associated with a significant (P < 0.05) improvement in overall 5-year cancer-specific survival for those patients with an R0 resection. Postoperative chemotherapy did not alter outcomes. Conclusions: R0 resection of the pelvic recurrence is the most significant factor affecting overall and disease-free survival. The surgery is complex and often highly morbid, and where possible patients should be given perioperative chemoradiotherapy. Further investigations are required to determine the role of adjuvant chemotherapy.

Anastomotic Leaks After Restorative Resections for Rectal Cancer Compromise Cancer Outcomes and Survival.

BACKGROUND: Anastomotic leaks after restorative resections for rectal cancer may lead to worse long-term outcomes. OBJECTIVE: The purpose of this study was to evaluate the best current evidence assessing anastomotic leaks in rectal cancer resections with curative intent and their impact on survival and cancer recurrence. DATA SOURCES: A meta-analysis was performed using MEDLINE, EMBASE, and Cochrane search engines for relevant studies published between January 1982 and January 2015. STUDY SELECTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was used to screen and select relevant studies for the review using key words “colorectal surgery; colorectal neoplasm; rectal neoplasm” and “anastomotic leak.” INTERVENTION: Anastomotic leak groups were compared with nonanastomotic leak groups. MAIN OUTCOME MEASURES: ORs were calculated from binary data for local recurrence, distant recurrence, and cancer-specific mortality. A random-effects model was then used to calculate pooled ORs with 95% CIs. RESULTS: Eleven studies with 13,655 patients met the inclusion criteria. This included 5 prospective cohort and 6 retrospective cohort studies. Median follow-up was 60 months. Higher cancer-specific mortality was noted in the leak group with an OR of 1.30 (95% CI, 1.04–1.62; p < 0.05). Local recurrences were more likely in rectal cancer resections complicated by anastomotic leaks (OR = 1.61 (95% CI, 1.25–2.09); p < 0.001). Distant recurrence was not more likely in the anastomotic leak group (OR = 1.07 (95% CI, 0.87–1.33); p = 0.52). LIMITATIONS: All 11 studies are level 3 evidence cohort studies. Additional sensitivity analyses were performed to minimize cross-study heterogeneity. CONCLUSIONS: Anastomotic leaks after restorative resections for rectal cancer adversely impact cancer-specific mortality and local recurrence.

Systematic Review of FDG-PET Prediction of Complete Pathological Response and Survival in Rectal Cancer

AbstractBackgroundAdvances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of 18F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. MethodsA search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. ResultsSeventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). ConclusionSUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.Advances in the management of rectal cancer have resulted in an increased application of multimodal therapy with the aim of tailoring therapy to individual patients. Complete pathological response (pCR) is associated with improved survival and may be potentially managed without radical surgical resection. Over the last decade, there has been increasing interest in the ability of functional imaging to predict complete response to treatment. The aim of this review was to assess the role of 18F-flurordeoxyglucose positron emission tomography (FDG-PET) in prediction of pCR and prognosis in resectable locally advanced rectal cancer. A search of the MEDLINE and Embase databases was conducted, and a systematic review of the literature investigating positron emission tomography (PET) in the prediction of pCR and survival in rectal cancer was performed. Seventeen series assessing PET prediction of pCR were included in the review. Seven series assessed postchemoradiation SUVmax, which was significantly different between response groups in all six studies that assessed this. Nine series assessed the response index (RI) for SUVmax, which was significantly different between response groups in seven series. Thirteen studies investigated PET response for prediction of survival. Metabolic complete response assessed by SUV2max or visual response and RISUVmax showed strong associations with disease-free survival (DFS) and overall survival (OS). SUV2max and RISUVmax appear to be useful FDG-PET markers for prediction of pCR and these parameters also show strong associations with DFS and OS. FDG-PET may have a role in outcome prediction in patients with advanced rectal cancer.

Surgery for Locally Recurrent Rectal Cancer: Tips, Tricks, and Pitfalls.

Rectal cancer can recur locally in up to 10% of the patients who undergo definitive resection for their primary cancer. Surgical salvage is considered appropriate in the curative setting as well as select cases with palliative intent. Disease-free survival following salvage resection is dependent upon achieving an R0 resection margin. A clear understanding of applied surgical anatomy, appropriate preoperative planning, and a multidisciplinary approach to aggressive soft tissue, bony, and vascular resection with appropriate reconstruction is necessary. Technical tips, tricks, and pitfalls that may assist in managing these cancers are discussed and the roles of additional boost radiation and intraoperative radiation therapy in the management of such cancers are also discussed.

Acute and chronic pseudo‐obstruction: a current update

Acute colonic pseudo‐obstruction (ACPO) and chronic intestinal pseudo‐obstruction (CIPO) are distinct clinical entities in which patients present similarly with symptoms of a mechanical obstruction without an occlusive lesion. Unfortunately, they also share the issues related to a delay in diagnosis, including inappropriate management and poor outcomes. Advancements have been made in our understanding of the aetiologies of both conditions. Several predisposing factors linked to critical illness have been implicated in ACPO. CIPO is a functional motility disorder, historically misdiagnosed, with unnecessary surgery being performed in many patients with dire consequences. This review discusses the pathophysiology, clinical and diagnostic features, and treatment of each. For ACPO, a safer pharmacological approach to treatment is presented in a modified up‐to‐date algorithm. The importance of CIPO as a differential diagnosis when seeing patients with recurrent admissions for abdominal pain and distention is also discussed, as well as specific indications for surgery. While surgery is often a last resort, the role of the surgeon in the management of both ACPO and CIPO cannot be undervalued. By characterizing each condition in a common review, the knowledge gleaned aims to optimize outcomes for these frequently complex patients.

Primary squamous cell carcinoma of the rectum: An update and implications for treatment

AIM To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCCs are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the optimal treatment remains as yet undefined, recent studies have demonstrated a global shift away from surgery towards definitive chemoradiotherapy as primary treatment. Pooled overall survival was calculated to be 86% in patients managed with chemoradiation compared with 48% for those treated traditionally with surgery. Furthermore, local recurrence and metastatic rates were 25% vs 10% and 30% vs 13% for the chemoradiation vs conventional treatment cohorts. CONCLUSION The changing paradigm in the treatment of rectal SCC holds great promise for improved outcomes in this rare disease.

No increase in colorectal cancer in patients under 50 years of age: a Victorian experience from the last decade

The study aimed to assess whether there has been an increase in the incidence of colorectal cancer (CRC) among young patients in Victoria and whether such cancers are more advanced at presentation.

Distal intestinal obstruction syndrome in cystic fibrosis: presentation, outcome and management in a tertiary hospital (2007–2012)

Cystic fibrosis (CF) can result in distal intestinal obstruction syndrome (DIOS) due to inspissated mucus. This paper describes the clinicopathological characteristics of adult CF patients with DIOS and assesses risk factors for surgery.