Browsing by Author "Chandrasinghe, P."

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Assessing tumor molecular profiling to guide treatments for patients with advanced female genital tract malignancy
(Impact Journals, 2017) Carter, P.; Alifrangis, C.; Cereser, B.; Chandrasinghe, P.; Del Bel Belluz, L.; Fotopoulou, C.; Frilling, A.; Herzog, T.; Moderau, N.; Tabassum, N.; Krell, J.; Stebbing, J.
Tumor molecular profiling has enabled selection of targeted therapies in a host of solid tumors. Here we used a retrospective clinical cohort, to evaluate the benefit of tailoring treatments for female genital tract malignancy, using tumor molecular profiles. Clinical outcome data for 112 patients was retrospectively separated into two groups. These either followed a matched treatment plan that incorporated at least one drug recommended according to their tumor profile and none that were expected to have no benefit (64 patients), or was unmatched with suggested treatments and received at least one drug that was anticipated to lack benefit for that tumor (48 patients). In the group of patients whose drugs matched those recommended by molecular profiling of their tumor, their overall survival was 593 days on average, compared to 449 days for patients that did not; removing drugs predicted to have no benefit from treatment regimens received after profiling increased survival by 144 days on average (P = 0.0265). In the matched treatment group, 30% of patients had died by the last time of monitoring, whereas this was 40% in the unmatched group (P = 0.2778). The IHC biomarker for the progesterone receptor was demonstrated to be prognostic for survival.
The benefit of tumor molecular profiling on predicting treatments for colorectal adenocarcinomas
(Impact Journals, 2018) Carter, P.; Alifrangis, C.; Chandrasinghe, P.; Cereser, B.; Del Bel Belluz, L.; Leo, C.A.; Moderau, N.; Tabassum, N.; Warusavitarne, J.; Krell, J.; Stebbing, J.
Complete migration of a composite mesh into small bowel incidentally found during laparotomy for colectomy in an asymptomatic patient: a case report
(BioMed Central, 2020) Chandrasinghe, P.; de Silva, A.; Welivita, A.; Deen, K.I.
BACKGROUND: Composite meshes are used for incisional hernia repair because they enable intraperitoneal mesh placement due to their dorsal surface, which is made of inert material. We report, for the first time, to our knowledge, a case of composite mesh migration detected incidentally during a laparotomy for colon cancer in an asymptomatic patient. CASE PRESENTATION: Our patient was a 71-year-old South Asian man who underwent ventral mesh repair following a postoperative complication after right hemicolectomy for colon cancer. The patient was diagnosed with a metachronous sigmoid cancer 5 years later, for which he underwent laparotomy. During laparotomy, a migrated mesh was incidentally found and extracted from his proximal ileum without any evidence of abscess or fistula formation. CONCLUSION: To our knowledge, this is the first report of an incidentally found migrated composite mesh from a bowel lumen in an asymptomatic patient. KEYWORDS: Case report; Composite mesh; Mesh complications; Mesh migration.
Correction: Assessing tumor molecular profiling to guide treatments for patients with advanced female genital tract malignancy
(Impact Journals, 2018) Carter, P.; Alifrangis, C.; Cereser, B.; Chandrasinghe, P.; Del Bell Belliz, Z.; Fotopoulou, C.; Frilling, A.; Herzog, T.; Moderau, N.; Tabassum, N.; Krell, J.; Stebbing, J.
[This corrects the article DOI: 10.18632/oncotarget.23675.]. Erratum for : Assessing tumor molecular profiling to guide treatments for patients with advanced female genital tract malignancy. [Oncotarget. 2017; 9(5):6007-6014]
Correction: Does molecular profiling of tumors using the Caris molecular intelligence platform improve outcomes for cancer patients?
(Impact Journals LLC, 2018) Carter, P.; Alifrangis, C.; Cereser, B.; Chandrasinghe, P.; Del Bel Belluz, L.; Herzog, T.; Levitan, J.; Moderau, N.; Schwartzberg, L.; Tabassum, N.; Wen, J.; Krell, J.; Stebbing, J.
This corrects the article DOI: 10.18632/oncotarget.24258.]. Erratum for Does molecular profiling of tumors using the Caris molecular intelligence platform improve outcomes for cancer patients? [Oncotarget. 2018 ;9(10):9456-9467]
Correction: The benefit of tumor molecular profiling on predicting treatments for colorectal adenocarcinomas
(Impact Journals LLC, 2018) Carter, P.; Alifrangis, C.; Chandrasinghe, P.; Cereser, B.; Del Bel Belluz, L.; Leo, C.A.; Moderau, N.; Tabassum, N.; Warusavitarne, J.; Krell, J.; Stebbing, J.
This corrects the article DOI: 10.18632/oncotarget.24257. Erratum for The benefit of tumor molecular profiling on predicting treatments for colorectal adenocarcinomas [Oncotarget. 2018 ;9(13):11371-11376]
Development of a model of 3D imaging for the pre-operative planning of TaTME
(Oxford University Press, 2018) Sahnan, K.; Pellino, G.; Adegbola, S.O.; Tozer, P.J.; Chandrasinghe, P.; Misovik, D.; Hompes, R.; Hart, A.L.; Warusavitarne, J.; Lung, R.F.
BACKGROUND:Transanal TME (TaTME) is a new addition to the approaches in rectal surgery. TaTME requires advanced technical skills and, more importantly, knowledge of the pelvic structures, planes, and spaces as they are encountered moving cephalad from the perineum. We have developed a technique for producing 3D reconstructions of the anorectum and associated anatomy, to aid peri-operative planning and understanding of the anatomy crucial to TaTME surgery. METHODS: A patient was scheduled for single incision laparoscopy surgery (SILS) TaTME completion proctectomy and ileoanal pouch formation for ulcerative colitis. Standard axial T2-weighted Spectral Attenuated Inversion Recovery (SPAIR) and sagittal T2-weighted MRI sequences were obtained and digital imaging and communications in medicine (DICOM) images were imported into a validated open-source segmentation software.1 A specialist consultant gastrointestinal radiologist manually segmented the following structures: sphincter complex; rectosigmoid colon; levator plate, bladder, ureters, urethra and prostate. Each mesh was imported into another open-source system, MeshLab V1.3.3.1 as Stereolithography (STL) files for mesh smoothing to be applied. Individual labels were applied to each anatomical structure. RESULTS: Segmentation took approximately 15 min and an additional 10 min was required for smoothing and applying colour and transparency of the anatomical structures to emphasise surgically relevant anatomy. In Figure (A) provides an overview of the anatomy showing a relatively straight and posterior direction of the rectum as it descends into the pelvis; (B) provides insight into the relation between internal sphincter/rectum and the prostate/urethra. Distance between structures and relative proximity can be easily understood. Figure (C) shows the clearance between low rectum and both ureters, whilst (D) shows an anterior oblique view of the sphincter complex and the urethra. Conclusions :Surgeons currently use a combination of MRI scans, reports and discussion with radiologists to better understand anatomy. The use of these reconstructions in the MDT, in clinic and in the operating theatre could be useful to better communicate complex rectal anatomy, identify areas of difficulty and aid surgical planning. Our reconstructions present a present a cost-neutral solution to better visualise the anatomy they represent the first step towards innovation in TaTME surgery.
Development of a model of three-dimensional imaging for the preoperative planning of TaTME
(Springer, 2018) Sahnan, K.; Pellino, G.; Adegbola, S.O.; Tozer, P.J.; Chandrasinghe, P.; Miskovic, D.; Hompes, R.; Warusavitarne, J.; Lung, P.F.C.
Does molecular profiling of tumors using the Caris molecular intelligence platform improve outcomes for cancer patients?
(Impact Journals, 2018) Carter, P.; Alifrangis, C.; Cereser, B.; Chandrasinghe, P.; Del Bel Belluz, L.; Herzog, T.; Levitan, J.; Moderau, N.; Schwartzberg, L.; Tabassum, N.; Wen, J.; Krell, J.; Stebbing, J.
We evaluated the effect of tailoring treatments based on predictions informed by tumor molecular profiles across a range of cancers, using data from Caris Life Sciences. These included breast carcinoma, colorectal adenocarcinoma, female genital tract malignancy, lung non-small cell lung cancer, neuroendocrine tumors, ovarian surface epithelial carcinomas, and urinary tract cancers.Molecular profiles using mostly immunohistochemistry (IHC) and DNA sequencing for tumors from 841 patients had been previously used to recommend treatments; some physicians followed the suggestions completely while some did not. This information was assessed to find out if the outcome was better for the patients where their received drugs matched recommendations.The IHC biomarker for the progesterone receptor and for the androgen receptor were found to be most prognostic for survival overall. The IHC biomarkers for P-glycoprotein (PGP), tyrosine-protein kinase Met (cMET) and the DNA excision repair protein ERCC1 were also shown to be significant predictors of outcome. Patients whose treatments matched those predicted to be of benefit survived for an average of 512 days, compared to 468 days for those that did not (P = 0.0684). In the matched treatment group, 34% of patients were deceased at the completion of monitoring, whereas this was 47% in the unmatched group (P = 0.0001).
Double single-port pan-proctocolectomy with transanal total mesorectal excision [TaTME] and ileal pouch-anal anastomosis [IPAA]: improvisation under limited resources
(College of Surgeons of Sri Lanka, 2020) Chandrasinghe, P.; Kumarage, S.
ABSTRACT: Novel surgical techniques fail to reach all parts of the world equally due to financial constraints. Non-availability of high-cost equipment in the developing world hinders progress. Transanal total mesorectal incision [TaTME] is a novel technique becoming popular world over due to many perceived benefits. Some of the equipment requirements prevent surgeons in resource-limited environments from taking up this technique. We describe the performance of a double single port panproctocolectomy with TaTME and ileal pouch-anal anastomosis for a patient with colitis-associated rectal cancer under improvised conditions at a tertiary care centre in Sri Lanka. Standard practice requires two laparoscopic stacks and an integrated air insufflator both of which are not available in the local setting. A flexible endoscope was used to replace the need for a second laparoscopic stack and a simple drainage bag connection to the standard insufflator to provide a stable pneumo-peritoneum. The patient had a rapid uneventful recovery. KEYWORDS: TaTME, Double single port, Innovation, Pouch surgery
Fistulizing Crohn's disease
(Mosby Inc., 2020) Lightner, A.L.; Ashburn, J.H.; Brar, M.S.; Carvello, M.; Chandrasinghe, P.; Van Overstraeten, A.D.B.; Fleshner, P.R.; Gallo, G.; Kotze, P.G.; Holubar, S.D.; Reza, L.M.; Spinelli, A.; Strong, S.A.; Tozer, P.J.; Truong, A.; Warusavitarne, J.; Yamamoto, T.; Zaghiyan, K.
No abstract available
Improving quality of life after pouch surgery with a dedicated nurse led follow up programme
(Wiely-Blackwell, 2016) Chandrasinghe, P.; Leo, A.; Alison, L.; Perry-Woodford, Z.; Warusavitarne, J.
AIM:Bowel function after ileal pouch affects the quality of life (QOL). The aim of the study was to assess if objective evaluation and specialised supportive care improves QOL after pouch surgery.METHOD: Consecutive patients who had an ileoanal pouch were invited to participate in a systematic follow-up regime led by specialised pouch nurse practitioners. The Cleveland global Quality of Life (CGQOL) and specific pouch related symptoms were documented at 6, 12, 24 and 52 weeks after ileostomy reversal. Pearson's Rho coefficient was used to assess the correlation between symptoms and CGQOL. RESULTS: Thirty-nine consecutive patients who had ileoanal pouch surgery were evaluated. Thirty-four had more than two visits and improvement in CGQOL (mean-1.36 ± 0.95) was seen in 27 (79%). There was reduction in CGQOL in 5 patients (15%) and no change in 2 (6%). Daytime frequency (DTF) significantly correlated with mean CGQOL (R = −0.7, P < 0.01). Twenty (59%) of 34 had reduced DTF after intervention. Nocturnal frequency only showed correlation with CGQOL up to 3 months. Incontinence had no impact on the QOL in this cohort. CONCLUSION: DTF has the highest impact on QOL in this cohort. Regular systematic specialised pouch care follow up may achieve better QOL.
Incidence, prevalence and trends in IBD
(CRC Press, 2018) Chandrasinghe, P.; Spinelli, A.; Warusavitarne, J.
The inflammatory bowel diseases (IBD), Crohn’s disease and ulcerative colitis, are inflammatory conditions of unknown aetiology that affect the gastrointestinal tract. In Saudi Arabia, an increasing incidence of IBD has been registered, and a comparable disease progression has been recognised. Disease location is a significant factor associated with the long-term outcome in IBD. Extra-intestinal manifestations are pathologically and clinically important entities in IBD. Mortality due to IBD may be caused by complications of acute flares of the disease, long-term complication of the disease or surgical complications. Surgery is required in patients with IBD mainly for intestinal complications. The natural history of IBD is difficult to assess in today’s context, as a majority patients with symptoms will be undergoing some form of treatment. The downward trend may have been the result of more comprehensive surveillance programmes established in many high-volume IBD centres. IBDs are common chronic conditions, which place a significant burden on the individual and community.
Investigating the benefits of molecular profiling of advanced non-small cell lung cancer tumors to guide treatments
(Impact Journals, 2018) Alifrangis, C.; Carter, P.; Cereser, B.; Chandrasinghe, P.; Belluz, L.D.B.; Lim, E.; Moderau, N.; Poyia, F.; Tabassum, N.; Zhang, H.; Krell, J.; Stebbing, J.
In this study we utilized data on patient responses to guided treatments, and we evaluated their benefit for a non-small cell lung cancer cohort. The recommended therapies used were predicted using tumor molecular profiles that involved a range of biomarkers but primarily used immunohistochemistry markers. A dataset describing 91 lung non-small cell lung cancer patients was retrospectively split into two. The first group's drugs were consistent with a treatment plan whereby all drugs received agreed with their tumor's molecular profile. The second group each received one or more drug that was expected to lack benefit. We found that there was no significant difference in overall survival or mortality between the two groups. Patients whose treatments were predicted to be of benefit survived for an average of 402 days, compared to 382 days for those that did not (P = 0.7934). In the matched treatment group, 48% of patients were deceased by the time monitoring had finished compared to 53% in the unmatched group (P = 0.6094). The immunohistochemistry biomarker for the ERCC1 receptor was found to be a marker that could be used to predict future survival; ERCC1 loss was found to be predictive of poor survival.
Long-term function after transanal versus transabdominal ileal pouch-anal anastomosis for ulcerative colitis: a multicenter cohort study
(Wiely-Blackwell, 2019) Chandrasinghe, P.; Carvello, M.; Wasmann, K.; Tanis, P.; Warusavitarne, J.; Spinelli, A.; Bemelman, W.
AIM:The novel transanal approach to ileal pouch-anal anastomosis (ta-IPAA) provides better exposure with lower short-term morbidity in ulcerative colitis (UC). The aim of this study was to assess the long-term outcomes after ta-IPAA versus abdominal IPAA (abd-IPAA) in UC. METHOD:This is a multicentre cohort analysis between March 2002 and September 2017. Patient characteristics, surgical details and postoperative outcomes were compared. The primary end-point was CGQL (Cleveland Global Quality of Life) score at 12 months. RESULTS:374 patients (100 ta-IPAA vs 274 abd-IPAA) were included. Mean CGQL scores were comparable between the two groups (0.75 ± 0.11 vs 0.71 ± 0.14; respectively, P = 0.1). Quality of life (7.71 ± 1.17 vs 7.30 ± 1.46; P = 0.04) and energy level (7.16 ± 1.52 vs 6.66 ± 1.68; P = 0.03) were significantly better after ta-IPAA, while the quality of health item was comparable (7.68 ± 1.26 vs 7.64 ± 1.44; P = 0.9655). Stool frequencies (> 10/24 h:22% vs 21%; P = 1.0) and major incontinence rates (27% vs 26%; P = 0.89) were similar. Thirty-day morbidity rates (33% vs 41%; P = 0.2) and anastomotic leak rates were comparable (6% vs 13%; P = 0.09). CONCLUSION: This study, for the first time, provides evidence of comparable long-term functional outcome of ta-IPAA vs abd-IPAA for UC.
Long-term function after transanal vs. transabdominal ileal pouch-anal anastomosis for ulcerative colitis: a multi-centre cohort study
(Oxford University Press, 2019) Chandrasinghe, P.; Carvello, M.; Wasmann, K.; Tanis, P.; Warusavitarne, J.; Spinelli, A.; Bemelman, W.
BACKGROUND:The transanal approach has been introduced in ileal pouch-anal (IPAA) surgery to gain better exposure for the rectal dissection. It has been shown to be safe with lower morbidity than the trans-abdominal approach. The aim of this study was to compare functional outcome of transanal ileal pouch-anal anastomosis (ta-IPAA) with transabdominal (abd-IPAA) approach for ulcerative colitis (UC) using the Cleveland Global Quality of Life (CGQL). METHODS: This is a multi-centre cohort of consecutive patients undergoing abd-IPAA or ta-IPAA for UC prospectively registered in the databases of three tertiary referral institutions between March 2002 to September 2017. Patient characteristics, surgical details and postoperative outcomes were retrieved. The primary end-point was pouch function determined by CGQL score. The questionnaire was administered to all patients with a functioning pouch for 12 months. RESULTS: Ninety-nine patients with ta-IPAA were compared with 274 patients with abd-IPAA. A defunctioning stoma was created at the time of pouch construction in 46 (46%) patients undergoing ta-IPAA and in 130 (47%) patients with abd-IPAA (p = 0.90). Thirty-day postoperative complications according to Clavien-Dindo classification (p = 0.22) as well as anastomotic leak rates (13% vs. 6%), abd-IPAA and ta-IPAA, respectively, were comparable (p = 0.09). Time to stoma closure did not differ between the two groups (abd-IPAA- 6 ± 7 vs. ta-IPAA- 5 ± 4 months; p = 0.72). Twelve months CGQL score was obtained for 251 patients in the abd-IPAA group and for 97 in ta-IPAA cohort. The CGQL index was comparable between the two groups (0.72 ± 0.15 vs. 0.75 ± 0.12; p = 0.07). Quality of health and energy level components were statistically higher for ta-IPAA (7.30 ± 1.53 vs. 7.73 ± 1.19, p = 0.01; 6.68 ± 1.74 vs. 7.17 ± 1.54, p = 0.01) while no difference was found for quality of life item (7.63 ± 1.52 vs. 7.62 ± 1.30, p = 0.73). Pouch failure (including defunction and excision) was reported in 40 of 298 (12%) patients undergoing abd-IPAA and in 1 patient (1%) having ta-IPAA during the follow-up period. CONCLUSIONS: ta-IPAA produces functional result comparable to transabdominal approach at 12 months after surgery.
The MACC1-SPON2 axis: a new biomarker and therapeutic target in colorectal cancer
(Nature Publishing Group, 2017) Chandrasinghe, P.; Stebbing, J.; Warusavitarne, J.
In this issue of the Journal, Schmid et al identify Spondin 2 (SPON2) as a prominent downstream signaling target of metastasis-associated in colon cancer 1 (MACC1) in colorectal cancer (CRC). It is shown that SPON2 mediates MACC1-induced CRC cell proliferation, invasion and metastasis in vitro and in vivo, while its high expression correlates with adverse disease free survival in clinical samples. Therefore, not only does this study shed further light into the complexity of colorectal carcinogenesis, but it also puts forward a potential novel prognostic biomarker to predict high-risk tumors before they metastasize. The MACC1/SPON2 axis may also have utility beyond an indicator of tumor aggressiveness and lends itself as a promising therapeutic target for colorectal and potentially other solid tumors.
Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans
(Impact Journals, 2018) Carter, P.; Alifrangis, C.; Cereser, B.; Chandrasinghe, P.; Del Bel Belluz, L.; Moderau, N.; Poyia, F.; Schwatzberg, L.S.; Tabassum, N.; Wen, J.; Krell, J.; Stebbing, J.
We used data obtained by Caris Life Sciences, to evaluate the benefits of tailoring treatments for a breast carcinoma cohort by using tumor molecular profiles to inform decisions. Data for 92 breast cancer patients from the commercial Caris Molecular Intelligence database was retrospectively divided into two groups, so that the first always followed treatment recommendations, whereas in the second group all patients received at least one drug after profiling that was predicted to lack benefit. The biomarker and drug associations were based on tests including fluorescent in situ hybridization and DNA sequencing, although immunohistochemistry was the main test used. Patients whose drugs matched those recommended according to their tumor profile had an average overall survival of 667 days, compared to 510 days for patients that did not (P=0.0316). In the matched treatment group, 26% of patients were deceased by the last time of monitoring, whereas this was 41% in the unmatched group (P=0.1257). We therefore confirm the ability of tumor molecular profiling to improve survival of breast cancer patients. Immunohistochemistry biomarkers for the androgen, estrogen and progesterone receptors were found to be prognostic for survival.
North Colombo diverticular disease snap shot audit (VISTA study): a collaborative research initiative
(The College of Surgeons of Sri Lanka, 2023) Chandrasinghe, P.; Ediriweera, E.P.D.S.; Niriella, M.; Ranwaka, C.; Fernando, A.; Gunawardena, H.; Kumarage, S.
INTRODUCTION Diverticulosis and diverticular disease (DD) is a common occurrence in clinical practice in the local setting with a lack of documented literature. A snapshot audit was conducted at North Colombo Teaching Hospital (NCTH) to ascertain the disease burden in clinical practice as a pilot study to assess feasibility and response rate for a nation wide snapshot audit. METHODOLOGY All surgical and gastroenterology units at NCTH were requested to enter the data between 1st January 2022 to 30th of June 2022 on all patients presenting with DD or those detected with diverticulosis during screening colonoscopy. Prospective data collection was done using RedCap© data capturing platform. RESULTS Out of the 8 units invited (general surgery – 5, GI surgery – 1, gastroenterology – 2), 5 units participated (general surgery – 2, GI surgery – 1, gastroenterology – 2); response rate is 62%. A total of 46 patient records (median age- 68 years; range 29- 86; female 51%) were received within 6 months. Of the total 54.3% had symptomatic uncomplicated diverticular disease (SUDD) while 33% were detected with diverticulosis at screening. Only 13% (n=6) required inward care (bleeding – 3, diverticulitis – 2, perforation – 1) and detected using colonoscopy in 4 and CT scan in 2. In the DD group, 20% (6/31) had complicated DD while 80% had Symptomatic Uncomplicated Diverticular Disease (SUDD). CONCLUSION In this pilot study, a majority of the patients with DD presented with SUDD while around 20% came with complicated DD. The response rate from collaborators was satisfactory. The secure online database usage is feasible and will be used for a national level study in the future to assess the disease burden in the healthcare setting in Sri Lanka.
Quality of life following curative surgery for colorectal cancer in a Sri Lankan cohort; North Colombo experience
(Springer, 2021) Godahewa, S.; Gunasekare, K.; Gajasinghe, S.; Kumarage, S.; Chandrasinghe, P.
BACKGROUND/AIM: Colorectal cancer (CRC) is the 4th commonest cancer in Sri Lanka. It is increasingly approached with a curative intent due to the advancements in the surgical and medical management. This has resulted in a large cohort of cancer survivors that needs to be managed. Quality of life (QOL) and patient reported outcomes in CRC survivors assist in identifying and managing unique issues in this population. This study aims to describe objectively measured quality of life after surgery for colorectal cancer in a South Asian population. METHODS: Patients who underwent surgery for CRC and are currently disease free were included. QOL was assessed using the translated and validated SF36 questionnaire (Sinhala) along with patient complaints. SF36 components were aggregated into physical component summery (PCS) and mental component summery (MCS). Patient reported symptoms were categorized in to organ function, life style, and psycho-sexual. RESULTS: A Total of 100 patients completed the survey (median age—61 years; range 25–86, female—56%). Of the total 65% were rectal cancers while 35% were colon cancers. QOL assessment reported a PCS of 0.64 and a MCS of 0.67 (Max- 1.0). There was no difference in QOL between rectal and colon cancers (PCS: rectal—0.64 vs colon—0.63, P = 0.9; MCS: rectal— 0.65 vs colon—0.66) or based on follow-up period (\5 years vs[ 5 years; P = 0.3 and 0.9). Organ function related problems were reported by 69% and increased frequency was the main complaint (27%). CONCLUSION: The QOL of a Sri Lankan cohort of CRC survivors is described. QOL did not differ between rectal and colon cancers. Neither PCS nor MCS had significantly improved over time following surgery.