Factors influencing local and distant recurrence following resection of periampullary cancer.

BACKGROUND: Recurrence of periampullary cancer after pancreatoduodenectomy is common. The aim of this study was to investigate patterns of recurrence, incidence, and factors associated with local and distant recurrences. METHODS: This retrospective, single-centre study included consecutive patients with periampullary cancer who underwent resection with curative intent from January 2012 to January 2018. Survival, patterns of recurrence, and factors associated with recurrences were analysed. RESULTS: Median overall survival (OS) and disease-free survival among 398 included patients was 58.4 and 49.5 months respectively. Twenty-three patients (5.8 per cent) developed isolated local recurrences (LR), 50 (12.6 per cent) developed LR along with distant metastasis (DM), and 103 (25.9 per cent) developed isolated DM. Median OS was 40.4 months for patients with isolated LR versus 23 months for those with DM (P < 0.001). Tumour subtype (distal common bile duct (CBD): odds ratio (OR) 6.18, 95 per cent c.i. 2.19 to 17.46) and node-positive status (OR 2.36, 1.26 to 4.43) were independently associated with higher rates of LR. The most common site for isolated LR was along the superior mesenteric artery (12 of 23 patients). Tumour subtype (distal CBD: OR 2.86, 1.09 to 7.52), nodal positivity (OR 2.46, 1.53 to 3.94), and presence of perineural invasion (OR 1.80, 1.02 to 3.18) were independently associated with DM. CONCLUSION: Isolated LR is associated with better survival than DM and occurs most commonly along the superior mesenteric artery.

Can Post-Treatment MRI Features Predict Pathological Circumferential Resection Margin (pCRM) Involvement in Low Rectal Tumors.

The MERCURY II study demonstrated the use of MRI-based risk factors such as extramural venous invasion (EMVI), tumor location, and circumferential resection margin (CRM) involvement to preoperatively predict pCRM (pathological CRM) outcomes for lower rectal tumors in a mixed group of upfront operated patients and patients who received neoadjuvant treatment. We aim to study the applicability of results of MERCURY II study in a homogeneous cohort of patients who received neoadjuvant chemoradiation (NACTRT) prior to surgery. After Institutional Review Board approval, post NACTRT restaging MRI of 132 patients operated for low rectal cancer between 2014 and 2018 were retrospectively reviewed by two radiologists for site of tumor, EMVI status, distance from anal verge (< 4 or > 4 cm), and mrCRM positivity. Findings were compared with post surgery pCRM outcomes using Fisher's exact test. Only 9/132(7%) patients showed pCRM involvement on histopathology, 8 of them being CRM positive on MRI (p = 0.01). The positive predictive value (PPV) of mrCRM positive status and pCRM status was 12.7% (95% CI: 9.7-16.5%), while the negative predictive value was 98.5% (95% CI: 91.4-99.8%) (p = 0.01). EMVI positive and anteriorly located tumors showed higher incidence of pCRM positivity but were not found to be significant (15% vs 5.2% and p = 0.13 and 8.6% vs 2.1% and p = 0.28, respectively). Unsafe mrCRM was the only factor significantly associated with pCRM positivity on post neoadjuvant restaging MRI. Tumors less than 4 cm from anal verge, anterior tumor location, and mrEMVI positivity did not show statistically significant results to predict pCRM involvement.

Outcomes of Definitive Treatment of Signet Ring Cell Carcinoma of the Rectum: Is Minimal Invasive Surgery Detrimental in Signet Ring Rectal Cancers?

The outcome of surgery for signet ring adenocarcinoma of rectum is suboptimal with high predilection for locoregional and peritoneal metastases. Lack of intercellular adhesion due to focal loss of epithelial cell adhesion molecule (EpCAM) may account for this. In such patients, whether minimal invasive surgery carries a high risk of dissemination by pneumoperitoneum and tumor implantation remains uncertain. The aim of this study was to compare the outcomes of patients undergoing minimally invasive surgery (MIS) versus open surgery in patients with signet ring cell adenocarcinoma of rectum. A retrospective study was conducted at a tertiary care center over 3 years on 39 patients undergoing open surgery and 40 patients undergoing MIS diagnosed with signet ring cell carcinoma (SRCC) identified from our surgical database. Patient characteristics in terms of demographics, clinicoradiological staging, neoadjuvant therapy, and type of surgery with morbidity were compared in the two groups. Data on patients undergoing adjuvant therapy and 3 years disease-free survival (DFS) and overall survival (OS) were analyzed. Recurrence patterns in both groups were separately identified as locoregional, peritoneal, or systemic. The number of patients undergoing surgery in the two arms was 40 (MIS) and 39 (open). In the MIS arm, mean DFS was 29 months whereas in the open arm, it was 25.8 months. The mean OS was 33.65 months for the MIS arm and that for the open arm was 36.34 months. This retrospective study reveals no significant difference in outcomes of surgery for signet ring cell rectal cancers with either MIS or open approach.

Clinical Utility of Staging Laparoscopy for Advanced Obstructing Rectal Adenocarcinoma: Emerging Tool.

The multimodal treatment for advanced rectal adenocarcinoma mandates accurate preoperative staging with contrast-enhanced computed tomography (CECT) of the thorax, abdomen, and pelvis, and magnetic resonance imaging (MRI) of the pelvis. Unlike gastric cancer, the role of staging laparoscopy (SL) in advanced colorectal cancer has not been evaluated. This study aims to evaluate the clinical value of SL in treatment decision-making for advanced rectal cancer (RC) with near or complete obstructing tumors. Observational review of colorectal database at Tata Memorial Hospital from January 2013 to December 2016 identified 562 patients diagnosed and treated for advanced RC. Of the 562 cases, 48.7% (274) were clinically and radiologically diagnosed of near or complete obstructing advanced RC. Medical records of 34% (94/274) who underwent SL with diversion stoma (DS) were analyzed. In the absence of ascites, extensive peritoneal deposits, and unresectable liver metastases on SL, a curative treatment was offered, which entailed neoadjuvant chemoradiation (NACTRT), whereas the cohort of patients with extensive peritoneal disease received palliative therapy. Of the 94 patients with advanced RC, conventional imaging studies staged 73.5% (69/94) cohort as non-metastatic locally advanced and 26.5% (25/94) had potentially resectable metastatic RC. Pre-therapeutic SL upstaged the disease by 26% (18/69) and 8% (2/25) in locally advanced and potentially resectable metastatic RC cohorts, respectively. Treatment decision changed in 21.2% (20/94) of the patients, and midline laparotomy was thus avoided. In our observational study, SL was found to be a safe and effective staging modality in RC; it detected occult peritoneal disease and prevented midline laparotomy in 21.2% of the cohort, which was of value to determine treatment strategy in patients with advanced RC before initiating NACTRT. SL and laparoscopic-assisted de-functioning stoma were associated with minimal morbidity and led to early initiation of NACTRT.

Chemo-Radiation After Upfront Rectal Resections-a Clinical Dilemma.

To compare the impact of adjuvant chemo-radiotherapy (ACRT) versus adjuvant chemotherapy (ACT) alone on recurrence and survival in patients with stage II and III rectal adenocarcinoma undergoing upfront curative resection. Prospective observational review of colorectal database at Tata Memorial Hospital from July 2010 to March 2015 identified 84 patients who underwent upfront curative resection for stage II or III rectal cancer. None of the patient received preoperative chemo-radiation. Of these, adjuvant chemo-radiotherapy was administered to 29 patients (ACRT group) and 55 patients received CAPEOX/FOLFOX-based adjuvant chemotherapy (ACT group) alone. At a median follow-up of 20 months, there were 10 recurrences (3 local recurrence) in the ACRT group and 15 (2 local recurrence) in ACT group. The estimated disease-free survival at 3 years in the ACRT group was 62.7% and in ACT group was 49.7% (p = 0.417) with an estimated 3-year overall survival of 74 and 78% in the ACRT and ACT group, respectively (p = 0.241). Subgroup analysis was performed after risk stratifying prognostic features (pT4, pN2, poor differentiation, involved resection margin). Our study does not show any benefit of ACRT over ACT on local control, disease-free and overall survival after upfront rectal cancer resection for low-risk stage II-III. In the subgroup analysis, local recurrence did not occur in patients who did not have poor prognostic features irrespective whether they received ACRT or ACT. Adjuvant chemo-radiation can be avoided in low-risk stage II-III rectal cancer after upfront resection.

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

AIM: 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. METHOD: This was a retrospective study of primary rectal cancer patients. RESULTS: Of 237 patients, 61 (21.5%) patients with nonmetastatic carcinoma rectum had iAMRF at baseline. Ten patients defaulted before completion of neoadjuvant chemoradiotherapy. After neoadjuvant chemoradiotherapy, 22 patients (43.1%) developed systemic metastases, seven patients (13.8%) were downstaged to free anterior mesorectal fascia and underwent total mesorectal excision (anterior resection/abdominoperineal resection) and the remaining 22 patients (43.1%) had persistent iAMRF. Thirteen patients with persistent iAMRF underwent ERR, whereas nine patients underwent TPE. The median duration of hospital stay in the TPE group was 13 days (10-26), whereas it was 7 days (5-21) in the ERR group. A clear circumferential resection margin, R0 resection, was achieved in all patients with TPE and ERR. After a median follow-up of 31.6 months, five patients with TPE (55.6%), four patients with ERR (30.7%) and three patients in the downstaged group (42.9%) developed systemic recurrence. None of the patients with TPE and the downstaged group developed local recurrence, whereas three patients with ERR (23.1%) developed local recurrence. Median disease-free survival was 12.3 months in the TPE group, 18.9 months in the ERR group and 10.6 months in the downstaged group, whereas mean overall survival was 36.2, 32.8 and 27.9 months, respectively. CONCLUSION: Although there is no significant difference in the overall survival and disease-free survival, ERR is associated with a high risk of local recurrence compared to TPE and the downstaged group.

Carcinoembryonic antigen directed PET-CECT scanning for postoperative surveillance of colorectal cancer.

AIM: During the follow-up of surgically resected colorectal cancer (CRC), positron emission tomography-contrast-enhanced computed tomography (PET-CECT) is indicated for asymptomatic elevation of carcinoembryonic antigen (CEA) > 5 ng/ml and no obvious site of recurrence on clinical examination and basic imaging. As an institutional policy, a PET-CECT scan was performed at our institute whenever (1) CEA levels rose above 5 ng/ml and (2) CEA values were doubled (even if the CEA level was < 5 ng/ml). Our aim was to correlate the range of CEA elevation with recurrence rates and to evaluate the diagnostic utility of PET-CECT scanning in this setting. METHOD: We retrospectively analysed all cases where a PET-CECT scan was performed for elevated CEA levels during surveillance visits after complete resection of the primary tumour followed by adjuvant therapy. This study was conducted from 1 January 2013 to 31 July 2015. RESULTS: In all, 104 patients underwent a PET-CECT scan for rising CEA values, and 62 patients (59.6%) were found to have recurrent disease. At CEA levels < 5, 5.1-10, 10.1-15, 15.1-50 and > 50 ng/ml, disease recurred in 10%, 45%, 70%, 94% and 100% patients, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of the PET-CECT scan were 92.7%, 95.2%, 96.2% and 90.9%, respectively. Elevation of CEA levels during follow-up was indicative of recurrence in 68% of the secretors and 45% of the non-secretors (based on baseline CEA status). CONCLUSION: In the setting of rising CEA levels during follow-up of patients with CRC, a PET-CECT scan is a valuable tool to detect recurrence, irrespective of the baseline CEA secretor status. The likelihood of recurrence of disease was directly proportional to the value of the raised CEA level.

Outcome of operable oral cavity cancer and impact of maintenance metronomic chemotherapy: A retrospective study from rural India.

BACKGROUND: Oral cavity cancer is the most common cancer among rural India. There is a paucity of data for outcomes of operable oral cavity cancer from rural India. Use of maintenance metronomic may delay or avoid relapse. AIM: To evaluate outcomes of operable oral cavity carcinoma and evaluate impact of maintenance metronomic chemotherapy. OBJECTIVES: To evaluate disease-free survival (DFS), overall survival (OS), and factors affecting the outcome in operable oral cavity cancer. MATERIALS AND METHODS: Data of patients diagnosed with oral cavity cancer registered between May 2008 and May 2014 were retrieved. Only those patients with operable oral cavity cancer and upfront definitive surgery were included in the study. Demographic profile, stage, tobacco consumption, adjuvant therapy, and pattern of failure were collected. Kaplan-Meir survival analysis was used to determine DFS and OS. Log-rank test was used to evaluate factors affecting outcome. RESULTS: Median follow-up is 24 months. Out of 335 patients, 225 (67%) had advanced operable cancer with 42/225 (18%) and 183/225 (82%) as Stages III and IVA, respectively. Buccal mucosa was the most common subsite (178/335, 53%) followed by tongue (63/335, 19%). Ninety-two percent patients were addicted to smokeless tobacco, whereas 27% were smokers. Median DFS is 13 months with 2 years relative DFS 32%. Median OS is 30 months, with 2 years OS of 54%. Metronomic adjuvant oral chemotherapy was given in 130/225 (58%); Stage III and IVA patients with median of 14 months (3-18 months). Use of metronomic chemotherapy improved DFS (8 vs. 14 months, P = 0.22) and OS (14 vs. 26 months, P = 0.04). CONCLUSION: Oral cavity cancer is a major health care problem in rural India. Presentation at advanced stage leads to suboptimal outcomes. Benefit of metronomic maintenance chemotherapy in locally advanced oral cavity needs to be further evaluated prospectively.

Multidisciplinary management of colorectal adenocarcinoma associated with anal fistula: an Indian series.

AIM: Adenocarcinomas associated with anal fistula are rare and often present at an advanced stage. They are often mistaken for commonly occurring benign diseases, leading to delayed diagnosis. Previous reports have predicted inferior oncological outcomes for these cases compared with sporadic rectal cancers. We are presenting our series of patients with colorectal adenocarcinoma associated with anal fistula who were treated with multimodality therapy at a tertiary cancer centre in India. METHOD: This was a retrospective review of a prospectively maintained database of patients treated at our centre between 1 July 2013 and 31 March 2015. Of the 15 patients included in the study, 11 had prior intervention in the form of seton placement or fistulotomy. Fourteen patients had circumferential resection margin (CRM) involvement at initial workup and hence were given neoadjuvant chemoradiotherapy (NACRT). None of the patients had distant metastasis and only 15% had regional nodal involvement. RESULTS: All 13 patients included in the final analysis underwent abdominoperineal excision (APE). Ten patients (73%) underwent extralevator APE. Plastic reconstruction in the form of a V-Y advancement flap for perineal closure was required in six patients (46%). On histopathological examination, a mucinous component was found to be present in 11 patients (73%). The quality of total mesorectal excision was complete in 92% patients. The CRM was free in 92% of patients. Median overall survival and disease-free survival were not reached. CONCLUSION: Colorectal adenocarcinomas associated with fistula are locally aggressive malignancies with a low incidence of lymph node involvement and distant metastasis. NACRT, wider resection in the form of extralevator APE, and liberal use of plastic reconstruction may result in favourable outcomes.