Claramae Shulyn Chia

Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis

Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.

Prognostic Significance of Invasion Depth in Oral Tongue Squamous Cell Carcinoma

Purpose: Staging for tongue carcinoma does not consider its depth of invasion. We aim to determine the prognostic significance of invasion depth in tongue cancer. Materials and Methods: Retrospective review of patients with tongue carcinoma who underwent curative surgery between 2002 and 2005; 67 patients were analyzed. Tumors were divided into 2 groups: group A = invasion depth <4 mm; group B = invasion depth ≥4 mm. Recurrence and survival rates were calculated for each group and compared. Results: The local recurrence rate in group B was significantly higher (10 vs. 29.7%, p = 0.048). Group A patients had a superior 5-year overall survival (68.8 vs. 41.6%, p = 0.012), disease-specific survival (67.1 vs. 41.1%, p = 0.026) and local recurrence-free survival (89.5 vs. 65.4%, p = 0.035). Five-year regional recurrence, locoregional recurrence and distant recurrence-free survival rates were not significantly different between the 2 groups (p = 0.390, p = 0.173 and p = 0.207). The impact of invasion depth on survival was maintained on multivariate analysis (p = 0.031). Conclusion: Invasion depth is an important prognostic indicator in tongue cancer.

Quality of life in patients with peritoneal surface malignancies after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND An increasing number of patients are presenting with peritoneal carcinomatosis and more centers are performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While morbidity and mortality are shown to be acceptable, quality of life after surgery should be assessed. METHODS 63 patients who had CRS and HIPEC from 2001 to 2012 and who were still alive and on follow up were included. The EORTC-QLQ-C30 was administered to the patients. RESULTS Median age was 53 years (14-71). 44% had ovarian primaries, 21% had appendicael primaries and 19% had colorectal primaries. Median follow-up was 1.08 years (0.06-9.8). The median time from surgery to the questionnaire was 1.3 years (0.24-10.18). There was no statistical difference in scores when comparing by age, gender, recurrence, gender, PCI score, presence of a complication and type of primary cancer. Scores were highest less than 6 months after surgery, dropped subsequently but rose again after 2 years. Our patients had better scores compared to a control group of outpatient cancer patients at our institution as well as the reference EORTC group. CONCLUSIONS In keeping with previous quality of life studies done for CRS and HIPEC patients, we have shown that our patients can achieve a good quality of life after CRS and HIPEC even with recurrent disease.

Does early post-operative intraperitoneal chemotherapy (EPIC) for patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) make a difference?

Abstract Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early post-operative intraperitoneal chemotherapy (EPIC). We compared the morbidities, overall survival (OS) and disease free survival (DFS) between two groups of patients who underwent CRS and HIPEC alone and with EPIC at our institution. Methods: A retrospective review of 111 patients with PC who were treated with CRS + HIPEC or CRS + HIPEC + EPIC in a single institution between January 2008 and April 2014 was performed. EPIC with 5-fluorouracil or paclitaxel was utilised, depending on the primary tumour. Results: Patients who received EPIC had a higher proportion of grade III and above post- operative complications (58% versus 25%; p = 0.048) and a longer duration of hospitalisation (16 days versus 13 days; p = 0.019) than patients without EPIC. There were no significant OS and DFS differences between the EPIC and no EPIC groups (log-rank p = 0.231 and p = 0.144, respectively). Conclusion: The use of EPIC after CRS + HIPEC for PC potentially results in increased morbidity and longer hospitalisation, and is unlikely to affect survival outcomes. Based on our experience, EPIC is not recommended after CRS and HIPEC.

201 consecutive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in a single Asian tertiary centre

Abstract Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We provide a review of a high-volume Asian institutes experience and survival outcomes with this procedure. Methods: Data were prospectively collected from 201 consecutive CRS and HIPEC procedures performed in a single institution between April 2001 and November 2015. Our primary endpoints were overall survival (OS) and disease-free survival (DFS), and secondary endpoints were morbidity and mortality. Results: 77% of patients were Chinese, 9% were Malay, 6% were Indian and 8% were other ethnicities. Primary tumours were colorectal (30%), ovarian (32%), appendiceal (20%), primary peritoneal (6.5%), mesothelioma (4.5%) and others (5%). The median peritoneal cancer index (PCI) was 12, and 92% of patients achieved a completeness of cytoreduction score (CC) of 0. High-grade morbidity occurred in 25.8% of cases, and there were no 30-day mortalities. At 5-years, the OS was 55.1% and DFS was 20.3%. Factors associated with improved OS on multivariate analysis were PCI <15 (p < 0.001) and a CC 0 (p = 0.016). Conclusions: The combined treatment of CRS and HIPEC is beneficial and is associated with reasonable morbidity and mortality in Asian patients with PC from colorectal, ovarian, appendiceal, primary peritoneal and mesothelioma primaries. Complete cytoreduction and extent of disease are the most important prognostic factors for survival.

Prognostic Relevance of the Peritoneal Surface Disease Severity Score Compared to the Peritoneal Cancer Index for Colorectal Peritoneal Carcinomatosis.

Background. Peritoneal Carcinomatosis Index (PCI) is a widely established scoring system that describes disease burden in isolated colorectal peritoneal carcinomatosis (CPC). Its significance may be diminished with complete cytoreduction. We explore the utility of the recently described Peritoneal Surface Disease Severity Score (PSDSS) and compare its prognostic value against PCI. Methods. The endpoints were overall survival (OS), progression-free survival (PFS), and survival less than 18 months (18 MS). Results. Fifty patients underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for CPC from 2003 to 2014, with 98% achieving complete cytoreduction. Median OS was 28.8 months (95% CI, 18.0–39.1); median PFS was 9.4 months (95% CI, 7.7–13.9). Univariate analysis showed that higher PCI was significantly associated with poorer OS (HR 1.11; 95% CI, 1.03–1.20) and PFS (HR 1.09; 95% CI, 1.03–1.14). Conversely, PSDSS was not associated with either endpoint. Multivariate analysis showed that PCI, but not PSDSS, was predictive of OS and PFS. PCI was also able to discriminate survival outcomes better than PSDSS for both OS and PFS. There was no association between 18 MS and either score. Conclusion. PCI is superior to PSDSS in predicting OS and PFS and remains the prognostic score of choice in CPC patients undergoing CRS/HIPEC.

Colorectal peritoneal carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: The experience of a tertiary Asian center

INTRODUCTION Compared with intravenous chemotherapy, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in patients with recurrent colorectal disease confined to the peritoneum. We report our experience with CRS and HIPEC for colorectal cancer patients with peritoneal carcinomatosis, evaluating prognostic factors for disease-free survival (DFS), overall survival (OS), and perioperative morbidity and mortality. METHODS All patients who underwent CRS and HIPEC were included in our study. Clinical characteristics, operative data, and 30-day morbidity and mortality were collected and evaluated. RESULTS Between January 2001 and December 2012, there were 35 consecutive patients who underwent CRS and HIPEC at our institution. Thirty-three patients (94%) had optimal cytoreduction. No 30-day mortality was reported, but 14 patients had postoperative complications. The median DFS was 9.4 months (95% confidence interval 5.5-18.7 months), and DFS at 1 year, 3 years, and 5 years were 43.8%, 22.3%, and 22.3%, respectively. The median OS was calculated to be 27.1 months (95% confidence interval 15.3-39.1), and the OS at 1 year, 3 years, and 5 years were 83.7%, 38.2%, and 19.1%, respectively. CONCLUSION CRS and HIPEC can provide survival benefit, with reasonable morbidity and mortality for Asian patients with peritoneal carcinomatosis from colorectal cancer. Patient selection and perioperative management of the patients are key to the success of the procedure.

A review of 111 anaesthetic patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION Cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC) is the treatment of choice for selected patients with peritoneal carcinomatosis, a previously lethal condition with dismal survival rates. METHODS We reviewed CRS and HIPEC procedures performed at our centre from January 1997 to December 2012, focusing on perioperative events and anaesthetic implications. RESULTS In total, 111 patients underwent 113 procedures. Mean age of the patients was 51.7 (range 14-74) years and 84.1% were women. Mean duration of surgery was 9 hours 10 minutes ± 2 hours 56 minutes. Most tumours were ovarian or colorectal in origin, and the mean peritoneal cancer index (PCI) score was 14.3 ± 8.9. Mean estimated blood loss was 1,481 ± 1,064 mL. Mean total intravenous fluids and blood products administered was 8,498 ± 3,941 mL. Postoperatively, 79.5% of the patients needed intensive care, as 75.2% of the 113 procedures required interval extubation. Patients with lower PCI scores were more likely to be extubated immediately after surgery (p < 0.05). 80.0% of patients had coagulopathy postoperatively, and this was associated with longer HIPEC duration (p < 0.05). Median lengths of intensive care unit and hospital stays were two days and 14 days, respectively. Longer duration of surgery significantly correlated with longer hospitalisation. Prolonged hospitalisation was due to nosocomial pneumonia, pleural effusions, respiratory failure, sepsis, surgical complications (such as anastomotic or wound dehiscence), and intra-abdominal infections. CONCLUSION The CRS and HIPEC technique is a major surgery with significant morbidity, as highlighted by the perioperative concerns observed in our study.

Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Abstract Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC. Methods: Retrospective analysis of a prospectively collected database of CRS–HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared. Results: Out of 214 CRS–HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I–II), and 49 patients (23%) suffered high-grade complications (grade III–V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens. Conclusions: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.

Gastric peritoneal carcinomatosis - a retrospective review

AIM To characterize patients with gastric peritoneal carcinomatosis (PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of care. METHODS We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral centre. RESULTS We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority (n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175 (64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. These patients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114 (66.7%), while cessation of chemotherapy occurred in 157 (91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not (10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not (8.7 mo vs 14.6 mo, P < 0.001). CONCLUSION Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their survival outcomes in the long run.