Shahid Khattak

Impact of acellular mucin pools on survival in patients with complete pathological response to neoadjuvant treatment in rectal cancer

BACKGROUNDnRarely, patients with pathological complete response (PCR) after neoadjuvant chemoradiotherapy demonstrate acellular mucin pools. The prognostic significance of this finding is controversial. The objective of this study was to determine impact of acellular mucin pools on disease free and overall survival in patients with complete pathological response to neoadjuvant chemoradiotherapy in rectal cancer.nnnMETHODSnOne hundred and seventy two patients received neoadjuvant chemoradiotherapy for rectal cancer and underwent surgery. Patients were divided into two groups based on presence of acellular mucin pools. Locoregional failures, distant failures and deaths were compared. Expected 5 year disease free and overall survival was calculated.nnnRESULTSnMedian follow-up was 36(4-94) months. Complete pathological response was identified in 35(20.3%) patients. Of these, 12(34.2%) had acellular mucin pools in resected specimen. Majority of mucin negative tumors were moderately differentiated (78% vs 25%) (Pxa0=xa00.005). Median overall survival for mucin positive and mucin negative tumors was 4(1.3-5.7) and 3.3(0.1-6.3) years respectively. Expected 5 year disease free and overall survival for mucin positive and mucin negative tumors was 73% and 89% (Pxa0=xa00.1) and 75% and 87% (Pxa0=xa00.4).nnnCONCLUSIONnAcellular mucin pools in rectal cancer following a PCR to neoadjuvant treatment do not impact survival.

Complete pathological response after neoadjuvant treatment in locally advanced esophageal cancer predicts long term survival: A retrospective cohort study ☆

BACKGROUND AND OBJECTIVESnEsophageal cancer incidence is gradually increasing worldwide. Studies have looked at the pathological stage rather than clinical stage as predictor of survival. We looked at patients with complete pathological response to compare their survival outcomes to those who had residual disease after neoadjuvant treatment.nnnMATERIALS AND METHODSnAll patients with esophageal cancer who underwent neoadjuvant treatment followed by resection at our institute were retrospectively reviewed. Overall survival and disease free survival were calculated for patients with complete pathological response and compared to those with residual disease using log rank test.nnnRESULTSnMean age of our patients was 51.08 years with standard deviation of 10.17 years. 39% belong to stage IIa while 5% belong to Stage IIb. 56% were Stage III. Final histopathological stage was recorded and both disease free and overall survival were calculated. 45% of our patients had complete pathological response. Patients with complete pathological response had mean survival of 62.73 monthsxa0±xa017.02 compared to 41.42 months for patients who had residual disease. 5 year disease free survival was 58%.nnnCONCLUSIONnComplete Pathological response significantly improves overall and disease free survival. It is also the predictor of long term survival.

Does prior percutaneous endoscopic gastrostomy alter post-operative outcome after esophagectomy.

BackgroundWith the introduction of neoadjuvant chemoradiotherapy in patients with esophageal carcinoma, nutritional access has become essential to counter deleterious effects of dysphagia. Current NCCN guidelines do not recommend PEG prior to esophagectomy in these patients, but there is little evidence for this recommendation. The objective of this study was to compare outcomes in patients who underwent esophagectomy with or without prior PEG placement.MethodsWe retrospectively reviewed 96 patients who underwent esophagectomy between 2005 and 2012 for esophageal carcinoma. Patients were divided into two groups; Group I (PEG +ve) and Group II (PEG −ve). Patient characteristics, operative variables, and post-operative complications were compared. χ2 and Fisher’s test were used for categorical, while t test was used for interval variables.ResultsMedian age was 51(18–70) years. Lower thoracic tumors were more common in Group I (69 vs. 63xa0%) (Pxa0=xa00.04) and more patients underwent minimally invasive surgery in this group (50 vs. 2.6xa0%) (Pxa0<xa00.0001). Mean blood loss (326 vs. 465xa0ml) (Pxa0=xa00.02) and ICU stay (1.6 vs. 4.3xa0days) (Pxa0=xa00.01) were significantly lower in Group I. There was no 30-day mortality in Group I versus 10.5xa0% in Group II (Pxa0=xa00.01). No significant difference in anastomotic leak and stricture rate was observed. Gastric conduit was used in all patients for reconstruction. One patient had malignancy in PEG site biopsy.ConclusionPercutaneous endoscopic gastrostomy before esophagectomy is safe and does not adversely impact post-operative outcomes.

Can Induction Chemotherapy before Concurrent Chemoradiation Impact Circumferential Resection Margin Positivity and Survival in Low Rectal Cancers

BACKGROUNDnDistance from anal verge and abdominoperineal resection are risk factors for circumferential resection margin (CRM) positivity in rectal cancer. Induction chemotherapy (IC) before concurrent chemoradiation (CRT) has emerged as a new treatment modification. Impact of IC before concurrent CRT on CRM positivity in low rectal cancer remains to be independently studied. The objective of this study was to determine CRM positivity in low rectal cancer, with and without prior IC, and to identify predictors of disease free and overall survival.nnnMATERIALS AND METHODSnPatients who underwent surgery for rectal cancer between 2005 and 2011 were retrospectively reviewed and divided into two groups. Group 1 received IC before CRT and Group 2 did not. Demographics, clinicopathological variables and CRM status were compared. Actuarial 5 year disease free survival (DFS), overall survival (OS) and independent predictors of survival were determined.nnnRESULTSnPatients in the IC group presented with advanced stage (Stage 3=89.2% versus 75.4%) (P=0.02) but a high rate of total mesorectal excision (TME) (100% versus 93.4%) (P=0.01) and sphincter preservation surgery (54.9 % versus 22.9%) (P=0.001). Patients with low rectal cancer who received IC had a significantly low positive CRM rate (9.2% versus 34%) (P=0.002). Actuarial 5 year DFS in IC and no IC groups were 39% and 43% (P=0.9) and 5 year OS were 70% and 47% (P=0.003). Pathological tumor size [HR: 2.2, CI: 1.1-4.5, P=0.01] and nodal involvement [HR: 2, CI: 1.08-4, P=0.02] were independent predictors of relapse while pathological nodal involvement [HR: 2.6, CI: 1.3-4.9, P=0.003] and IC [HR: 0.7, CI: 0.5-0.9, P=0.02] were independent predictors of death.nnnCONCLUSIONSnIn low rectal cancer, induction chemotherapy before CRT may significantly decrease CRM positivity and improve 5 year overall survival.

Outcome of rectal cancer in patients aged 30 years or less in the Pakistani population.

BACKGROUNDnThe incidence of rectal cancer is increasing in younger age groups. Limited data is available regarding survival outcome in younger patients with conflicting results from western world. The goal of this study was to determine survival in patients with rectal cancer<30 years of age and compare it with their older counterparts in the Pakistani population.nnnMATERIALS AND METHODSnA retrospective chart review of patients operated for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided into two groups, Group 1 aged ≤30 years and Group 2 aged >30 years. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year survival was calculated using Kaplan Meier curves and significance was determined using the Log rank test.nnnRESULTSnThere were 38 patients in group 1 and 144 in group 2. A significantly high number of younger patients presented with poorly differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus 57% in groups I and II, respectively (p=0.05). Disease free survival was 37% versus 52% and was significantly different (p=0.007).nnnCONCLUSIONSnEarly onset rectal cancer is associated with poor pathological features and a worse outcome in Pakistani population.

Minimally Invasive Esophagectomy for Esophageal Cancer: The First Experience from Pakistan

Background. Two common procedures for esophageal resection are Ivor Lewis esophagectomy and transhiatal esophagectomy. Both procedures have high morbidity rates of 20–46%. Minimally invasive esophagectomy has been introduced to decrease morbidity. We report initial experience of MIE to determine the morbidity and mortality associated with this procedure during learning phase. Material and Methods. Patients undergoing MIE at our institute from January 2011 to May 2013 were reviewed. Record was kept for any morbidity and mortality. Descriptive statistics were presented as frequencies and continuous variables were presented as median. Survival analysis was performed using Kaplan Meier curves. Results. We performed 51 minimally invasive esophagectomies. Perioperative morbidity was in 16 (31.37%) patients. There were 3 (5.88%) anastomotic leaks. We encountered 1 respiratory complication. Reexploration was required in 3 (5.88%) patients. Median operative time was 375 minutes. Median hospital stay was 10 days. The most frequent long-term morbidity was anastomotic narrowing observed in 5 (9.88%) patients. There were no perioperative mortalities. Our mean overall survival was 37.66 months (95% confidence interval 33.75 to 41.56 months). Mean disease-free survival was 24.43 months (95% CI 21.26 to 27.60 months). Conclusion. Minimally invasive esophagectomy, when performed in the learning phase, has acceptable morbidity and mortality.

Impact of lymph node ratio and number on survival in patients with rectal adenocarcinoma after preoperative chemo radiation

BACKGROUNDnRetrieval of <12 lymph nodes after proctectomy and preoperative chemoradiation (C-XRT) may improve survival in good risk patients. The objective of this study was to determine impact of <12 retrieved lymph nodes and lymph node ratio (LNR) on survival in a population with certain poor prognostic features for rectal cancer.nnnMETHODSnPatients who underwent surgery for rectal adenocarcinoma between 2005 and 2011 were divided them into <12 or >12 lymph node groups. The LNR groups were based on interquartile range. Clinicopathological and treatment outcomes were compared. Expected 5 year disease free and overall survival was calculated. Cox proportional hazard model was used to determine independent predictors.nnnRESULTSnMore patients in <12 lymph nodes removed group had low tumors (<5 cm from anal verge) (75.5% versus 60.7%) (P=0.03) and underwent abdominoperineal resection (59.1% versus 42.9%) (P=0.02). Overall survival (OS) and disease free survival (DFS) was not different [(56% and 52% (P=0.7)] [(50% and 57% (P=0.5)]. LNR<0.15 was independent predictor of DFS while LNR ratio<0.12 for OS on multivariate analysis.nnnCONCLUSIONnLNR and not number of retrieved nodes impacts survival in younger patients with predominance of anorectal tumors after C-XRT. A specific LNR cutoff remains to be defined.

Impact of Time Interval Between Chemoradiation and Surgery on Pathological Complete Response and Survival in Rectal Cancer

BACKGROUNDnLimited data are available regarding the impact of time duration between chemoradiation (CRT) and surgery on pathological complete response (PCR). A PCR translates into better overall and disease free survival. The objective of this study was to determine effect of time duration on outcome after preoperative CRT in rectal cancer.nnnMATERIALS AND METHODSnA retrospective review of patients undergoing operations for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided in two groups: Group 1 underwent surgery in ≤ 8weeks post neoadjuvant CRT and Group 2 after 8 weeks. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year overall survival and disease free survival was calculated using Kaplan Meier curves and significance was determined using the log rank test.nnnRESULTSnThere were 66 patients in group 1 and 93 in group 2. No significant difference in PCR was observed between the two. However, estimated 5 year DFS was significantly higher in Group 1 (66.7%) as compared to Group 2 (53.8%) (P=0.04). Estimated overall 5 year overall survival was not significantly different at 68.2% versus 54.3% (P= 0.09).nnnCONCLUSIONSnDelaying surgery more than 8 weeks after preoperative CRT does not impact for PCR in rectal cancer.

Stem Cell Organoids in Primary Cultures of Human Non-Malignant and Malignant Colon

Aims: A sub-population of cells named cancer stem cells (CSCs) that initiate and promote tumour growth have been demonstrated to exist in several malignancies including colon carcinoma. The objective of our pilot study was to isolate CD133+CD26+CD44+ CSCs from patient colon tumours, culture spheres or organoids and observe their proliferation in primary cultures. Parallel cultures of non-cancer controls from colon normal lining and nonadenomatous polyps were set up. n nMethods: Magnetic activated cell sorting was used to isolate CD133+CD26+CD44+ cell populations followed by primary cell culturing under stem cell culture conditions. Number, cells/organoid and daughter generations of organoids were calculated using phase contrast microscope. Trypan blue exclusion method was used to test the viability of the cells. n nResults: Both colon tumour and colon non-adenomatous polyp formed floating organoids in suspension; however non-adenomatous polyp cultures did not show self-renewal properties for more than 1 passage. Normal colon singlecell suspension did not create organoids. Metastatic colon tumours rapidly produce cancer cell organoids in less than 24 hours in larger numbers compared to non-metastatic colon tumours (1-3 weeks). Metastatic colon tumour organoids have the ability for proliferation for upto five daughter generations in primary culture compared to three generations for those grown from non-metastatic tumours. n nConclusions: This in vitro CSC organoid model will help study colon cancer biology, in particular providing a valuable source of primary cell-derived tissue for studying personalized molecular profiling using ‘omics strategies to direct therapeutic intervention.

Morbidity analysis in minimally invasive esophagectomy for oesophageal cancer versus conventional over the last 10 years, a single institution experience.

Background: There has been an increasing inclination towards minimally invasive esophagectomies (MIEs) at our institute recently for resectable oesophageal cancer. Objectives: The purpose of the present study is to report peri-operative and long-term procedure specific outcomes of the two groups and analyse their changing pattern at our institute. Methods: All adult patients with a diagnosis of oesophageal cancer managed at our institute from 2005 to 2015 were included in this retrospective study. Patients demographic and clinical characteristics were recorded through our hospital information system. The cohort of esophagectomies was allocated into two groups, conventional open esophagectomy (OE) or total laparoscopic MIE; hybrid esophagectomies were taken as a separate group. The short-term outcome measures are an operative time in minutes, length of hospital and Intensive Care Unit (ICU) stay in days, post-operative complications and 30 days in-hospital mortality. Complications are graded according to the Clavien-Dindo classification system. Long-term outcomes are long-term procedure related complications over a minimum follow-up of 1 year. Trends were analysed by visually inspecting the graphic plots for mean number of events in each group each year. Results: Our results showed no difference in mortality, length of hospital and ICU stays and incidence of major complications between three groups on uni- and multi-variate analysis (P > 0.05). The operative time was significantly longer in MIE group (odds ratio [OR]: 1.66, confidence interval [CI]: 2.4–11.5). The incidence of long-term complication was low for MIE (OR: 1.0, CI: 133–1.017). However, all post-operative surgical outcomes trended to improve in both groups over the course of this study and stayed better for MIE group except for the operative time. Conclusion: MIE has overall comparable surgical outcomes to its conventional counterpart. Furthermore, the peri-operative outcomes tend to improve in our centre with the maturation of program and experience.