Ashwin Desouza

Down-staging following neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: Does timing of surgery really matter?

Background: Neoadjuvant chemoradiotherapy (NACTRT) improves local recurrence rate in locally advanced (LA) rectal cancer with no survival benefit. Pathological complete response (pCR) post-NACTRT is associated with improved outcome. Debate is ongoing as to when would be the opportune time to operate. Aim: To determine if greater down-staging can be achieved by a longer time interval from NACTRT to surgery (tumor regression score [TRS]) and whether this would impact sphincter saving surgery rates and early relapse rates. Materials and Methods: A retrospective analysis of a prospectively maintained database of patients with LA rectal adenocarcinoma treated from January 2012 to August 2013 was carried out. One hundred and ten patients who completed NACTRT (50 Gy/25 fractions with capecitabine 825 mg/m2 twice daily) followed by surgical resection were included. For response evaluation patients were divided into two groups, Group 1 (TRS ≤60 days, n = 42) and 2 (TRS >60 days, n = 68). Tumor down-staging, pCR rate, tumor regression grade (TRG) post-NACTRT and relapse rates were correlated with TRS. Results: Of 110 patients (median age: 49 years (21-73), 71% males; 18 (16.5%) with signet ring histology) 96% patients underwent an R0 resection. Post-NACTRT, CR was attained in 5 (4.5%), partial response in 98 (89%) and stable disease in 7 (6.4%) patients. Median time from completion of NACTRT to surgery was 64.5 days (6-474). Median lymph nodes harvested were 10 (1-50). Overall, 22 (20%) patients achieved pCR. 26 (62%) patients in Group 1 compared to 36 (53%) in Group 2 underwent sphincter sparing surgery (SSS) (P = 0.357). Six patients (14%) in Group 1 and 16 (24%) in Group 2 achieved pCR (P = 0.24). Median TRG in both groups was three. Conclusion: Timing of surgery following NACTRT for LA rectal cancer does not influence pathological response, ability to perform SSS or disease-free survival. There is no incremental benefit of delaying the surgery though this needs to be confirmed in a prospective randomized trial.

Adenocarcinoma of the Rectum-A Composite of Three Different Subtypes With Varying Outcomes?

INTRODUCTION Adenocarcinoma of the rectum has been classified by the World Health Organization into various histologic subtypes. We analyzed the effect of the histologic subtype (classic, signet ring cell, and mucinous) on the clinical outcomes of patients with rectal cancer. We hypothesized that clinicopathologic outcome measures such as tumor margins, tumor regression grade, recurrence rate, and survival would vary with the histologic subtype. MATERIALS AND METHODS We conducted a retrospective analysis of a prospectively maintained database. All patients with stage I-III rectal adenocarcinoma were included. RESULTS From May 2010 to August 2013, 273 patients underwent curative resection. Both mucin-secreting variants were more common in younger patients and presented at a more advanced stage. Also, 54% and 48% of those with signet ring cell carcinoma (SRCC) and mucinous adenocarcinoma (MAC) had node-positive disease compared with the rate in the classic variant (30%). Circumferential resection margin positivity was 24% with MAC and 19% with SRCC compared with 4% with the classic variant. Disease-free survival for those with the classic and mucinous variants was 38.5 and 37.4 months, respectively. In contrast, it was 28.6 months in the SRCC group. The overall survival did not differ significantly. CONCLUSION Rectal adenocarcinoma presents as a spectrum of disease, with progressively worsening outcomes from classic to MAC to SRCC. These aggressive variants might warrant more aggressive resection. These data from the Indian subcontinent differ from the published data from Western countries.

Is Laparoscopic Surgery the Standard of Care for GI Luminal Cancer

As surgeons in India strive to keep pace with the technical advances in the field of laparoscopic surgery, we endeavor to evaluate the mounting global evidence regarding laparoscopic gastric and colorectal resections for cancer. We seem to be riding on the crest of excellence in traditional open surgery for gastrointestinal malignancies, opening avenues for research and for the establishment of practice guidelines in laparoscopic surgery. Results from available trials along with those from ongoing studies are paving the path toward the acceptance and standardization of these procedures. What must be ascertained is whether sound oncological principles, which are ultimately exhibited by long-term outcomes, are being preserved while garnering the established benefits of minimally invasive surgery.

Laparoscopic Versus Open Approach for Intersphincteric Resection—Results from a Tertiary Cancer Center in India

The study aims to compare open intersphincteric resection (OISR) with laparoscopic intersphincteric resection (LISR) in terms of short-term oncological and clinical outcomes. This is a retrospective review of a prospectively maintained database including all the patients of rectal cancer who underwent intersphincteric resection (ISR) at Tata Memorial Centre between 1st July 2013 and 30th November 2015. Short-term oncological parameters evaluated included circumferential resection margin involvement (CRM), distal resection margin involvement, and number of nodes harvested. Perioperative outcomes included blood loss, length of hospital stay and 30-day postoperative morbidity and mortality. Chi-square test was used to compare the results between the two groups. Thirty nine cases of OISR and 34 cases of LISR were included in the study. Median BMI was higher in LISR group; otherwise, the two groups were comparable in all aspects. There were no conversions in LISR group. CRM involvement was seen in four patients (10%) in the conventional group compared to none in the LISR group. Median hospital stay was comparable between the two groups. Laparoscopic ISR is safe and can be performed with low conversion rate in selected group of patients.

Selective extra levator versus conventional abdomino perineal resection: experience from a tertiary-care center

BACKGROUND To compare extra levator abdomino perineal resection (ELAPER) with conventional abdominoperineal resection (APER) in terms of short-term oncological and clinical outcomes. METHODS This is a retrospective review of a prospectively maintained database including all the patients of rectal cancer who underwent APER at Tata Memorial Center between July 1, 2013, and January 31, 2015. Short-term oncological parameters evaluated included circumferential resection margin involvement (CRM), tumor site perforation, and number of nodes harvested. Peri operative outcomes included blood loss, length of hospital stay, postoperative perineal wound complications, and 30-day mortality. The χ(2)-test was used to compare the results between the two groups. RESULTS Forty-two cases of ELAPER and 78 cases of conventional APER were included in the study. Levator involvement was significantly higher in the ELAPER compared with the conventional group; otherwise, the two groups were comparable in all the aspects. CRM involvement was seen in seven patients (8.9%) in the conventional group compared with three patients (7.14%) in the ELAPER group. Median hospital stay was significantly longer with ELAPER. The univariate analysis of the factors influencing CRM positivity did not show any significance. CONCLUSIONS ELAPER should be the preferred approach for low rectal tumors with involvement of levators. For those cases in which levators are not involved, as shown in preoperative magnetic resonance imaging (MRI), the current evidence is insufficient to recommend ELAPER over conventional APER. This stresses the importance of preoperative MRI in determining the best approach for an individual patient.

Major Gastrointestinal Cancer Resections in the Elderly in India: Poised for Future Challenges.

Background: There are no data on surgical outcomes of major gastrointestinal cancer resections in the expanding Indian oncogeriatric population. Methods: A prospective database of patients who underwent major gastrointestinal cancer resections during varying time periods (2006-2014) was analyzed retrospectively. Results: Two thousand six hundred and forty three patients with a median age of 53 were analyzed. Four hundred and seventy two (17.9%) patients were aged ≥65 years and 235 (8.9%) patients were ≥70 years. Mortality rates were not significantly higher in the elderly (≥65 years) or the very elderly (≥70 years) when compared to younger controls, being 2.8 vs. 1.6% (p = 0.09) and 3.0 vs. 1.7% (p = 0.162) respectively. Overall morbidity was similar for patients ≥65 or <65 years (24.2 vs. 21.7%, p = 0.253), but was higher in patients ≥70 years (29.8 vs. 21.4%, p = 0.003). The incidence of severe complications, however, was not significantly greater in this age group (13.2 vs. 12.5%, p = 0.74). Conclusions: Major gastrointestinal cancer resections in the elderly Indian population, though uncommon, are safe when performed at experienced high volume centres. These results should serve as a starting point for the gradual development of dedicated oncogeriatric programs in the Indian subcontinent.

Pulmonary metastasectomy of colorectal cancer origin: Evaluating process and outcomes: KUMAR et al.

This study was undertaken to evaluate the effect of change in policy of computed tomography (CT) scan of the thorax in staging and follow‐up of colorectal cancer (CRC). Another objective was to review the outcomes following pulmonary metastasectomies (Pmets) and to determine the prognostic factors affecting outcomes.

Persistent involvement of anterior mesorectal fascia in carcinoma rectum - extended resection of rectum vs total pelvic exenteration: results from a single-centre retrospective study

Involvement of the anterior mesorectal fascia (iAMRF) after neoadjuvant treatment leads to either resection of the involved organ alone [extended resection of the rectum (ERR)] or total pelvic exenteration (TPE). The purpose of this study was to compare the rate of recurrence and survival of patients undergoing ERR or TPE for iAMRF after neoadjuvant treatment. The outcome of patients who underwent total mesorectal excision after downstaging was also compared.

Impact of histological subtype on treatment outcomes in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation

Colorectal cancer is the third most common cancer in men (10.0% of all cancers) and the second most common in women (9.4% of all cancers). More than half of these cases are from developed countries [1]. Various histologic subtypes of this cancer have been described. Mucinous adenocarcinomas constitute 5–15% and signet ring cell carcinomas constitute 1% of all colorectal adenocarcinomas [2]. Each histological subtype has characteristic clinical presentation and prognosis associated with it. Several studies have shown signet cell histology to be a particularly poor prognostic marker in colorectal carcinoma [3,4]. There are very few studies reporting the impact of histological subtypes on outcomes in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACTRT). We retrospectively evaluated 205 consecutive LARC patients treated with curative intent between 1 January 2013 and 31 December 2014 at a tertiary hospital in India. All patients received long course NACTRT (50Gy/25# along with concurrent capecetabine) after discussion in the multidisciplinary joint clinic, followed by clinico-radiological reevaluation at 4–6 weeks. Patients who had threatened circumferential resection margin (CRM) or local disease progression during treatment were offered additional systemic therapy (4-6# CAP-OX/FOL-FOX) and were again re-assessed for surgery. The study population was grouped into three histological groups (Group A – Signet cell adenocarcinoma, Group B – Mucinous adenocarcinoma, and Group C – non-signet–nonmucinous adenocarcinoma, {NSNM}). Groups A, B, and C had 31, 35, and 139 patients, respectively. The median age at the presentation for the whole cohort was 44 years and the median follow up time was 3 years. These three groups were compared with respect to post-NACTRT response, recurrence pattern, disease-free survival (DFS), and overall survival (OS). Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 20.0 IBM Corp (Armonk, NY, USA). Chi-square or Fisher’s test was used for comparing frequencies between groups. The log-rank test was used to compare Kaplan–Meier survival curves. All tests were two-sided and a p value <.05 was considered statistically significant (Figure 1). The patient-, treatment-, and outcomes-related factors of the study cohort are shown in Tables 1–3, respectively. CRM was positive in six patients (4%), proximal and distal resection margin was negative in all the patients undergoing surgery. Overall pathological complete response rate (pCR) was 19% for the entire cohort and it was 23%, 27%, and 15% for the Groups A, B, and C, respectively. Recurrence rates were 19%, 29%, and 24% in Groups A, B, and C respectively. DFS was 22 months, 30 months, and 35 months in Groups A, B, and C, respectively. The difference between Groups A and B was not significant but between Group A and C and B and C were significant (p< .001). OS was 25 months, 38 months, and 40 months in Groups A, B, and C, respectively. The difference between Groups A and B was not significant but between Groups A and C and B and C was significant (p< .001). To our knowledge, this study is the first Indian study, describing the impact of different histological subtypes on treatment outcomes in LARC patients. Few previously published studies from the West have suggested poor response rates and outcomes in mucinous adenocarcinomas treated with NACTRT [5]. However, with improvements in surgical techniques, and when adequate CRM was obtained, it was found that there was no difference in DFS and OS [6]. Tata Memorial Center being a tertiary referral cancer center, percentage of advanced disease at presentation is higher and can be a reason for inherent selection bias. This can account for the fact that the percentage of signet cell carcinomas is much higher in our cohort compared with international data. Signet ring histology has long been known to have a poorer prognosis compared with other histologies. However, after NACTRT, pCR rates were quite high in this histology. However, this did not translate into higher OS. On the other hand, 23% patients in this histology group progressed on NACTRT, and received additional neoadjuvant chemotherapy. The concept of total neoadjuvant therapy is being actively researched currently. It presumably tackles the micro-metastases early by reducing sequencing delays in the administration of systemic therapy. It also improves the tolerability of therapy and ensures effective delivery of treatment prior to surgery

Metastatic anorectal melanomas – An exploratory retrospective analysis on the benefits of systemic therapy versus best supportive care in a resource-limited setting from India

Aim: Data regarding the optimal management of metastatic anorectal melanoma (mARM) is scarce. The primary aim was to evaluate the potential benefits of systemic therapy in mARM. Materials and Methods: This is a retrospective analysis of all mARM who presented between July 2013 and June 2015 at the Department of GI Medical Oncology, Tata Memorial Hospital. Results: Of a total of 37 patients, twelve patients were planned for best supportive care (BSC) only while the remaining 25 patients received systemic therapy. The median overall survival (OS) for the whole cohort was 27 weeks. The OS was significantly better in patients who received first-line therapy as compared to those who were offered BSC (median OS: 14 vs. 33 weeks; P = 0.04). Patients with PS of 1 did significantly better than PS of 2 more (OS 70 vs. 17 weeks; P = 0.015). Conclusion: mARM should be offered chemotherapy, especially in good performance patients. Paclitaxel/Platinum or Capecitabine/Temozolomide regimens can be considered as the preferred regime in the resource-limited setting where immunotherapy may not be a feasible option.