Curative-intended Surgery Research Articles

Time From Colorectal Cancer Surgery to Adjuvant Chemotherapy

The timing of adjuvant chemotherapy after surgery for colorectal cancer and its association with long-term outcomes have been investigated in national cohort studies, with no consensus on the optimal time from surgery to adjuvant chemotherapy. To analyze the association between the timing of adjuvant chemotherapy after surgery for colorectal cancer and disease-free survival. This is a post hoc analysis of the phase 3 SCOT randomized clinical trial, from 244 centers in 6 countries, investigating the noninferiority of 3 vs 6 months of adjuvant chemotherapy. Patients with high-risk stage II or stage III nonmetastatic colorectal cancer who underwent curative-intended surgery were randomized to either 3 or 6 months of adjuvant chemotherapy consisting of fluoropyrimidine and oxaliplatin regimens. Those with complete information on the date of surgery, treatment type, and long-term follow-up were investigated for the primary and secondary end points. Data were analyzed from May 2022 to February 2024. In the post hoc analysis, patients were grouped according to the start of adjuvant chemotherapy being less than 6 weeks vs greater than 6 weeks after surgery. The primary end point was disease-free survival. The secondary end points were adverse events in the total treatment period or the first cycle of adjuvant chemotherapy. A total of 5719 patients (2251 [39.4%] female; mean [SD] age, 63.4 [9.3] years) were included in the primary analysis after data curation; among them, 914 were in the early-start group and 4805 were in the late-start group. Median (IQR) follow-up was 72.0 (47.3-88.1) months, with a median (IQR) of 56 (41-66) days from surgery to chemotherapy. Five-year disease-free survival was 78.0% (95% CI, 75.3%-80.8%) in the early-start group and 73.2% (95% CI, 72.0%-74.5%) in the late-start group. In an adjusted Cox regression analysis, the start of adjuvant chemotherapy greater than 6 weeks after surgery was associated with worse disease-free survival (hazard ratio, 1.24; 95% CI, 1.06-1.46; P = .01). In adjusted logistic regression models, there was no association with adverse events in the total treatment period (odds ratio, 0.82; 95% CI, 0.65-1.04; P = .09) or adverse events in the first cycle of treatment (odds ratio, 0.77; 95% CI, 0.56-1.09; P = .13). In this international population of patients with high-risk stage II and stage III colorectal cancer, starting adjuvant chemotherapy more than 6 weeks after surgery was associated with worse disease-free survival, with no difference in adverse events between the groups. isrctn.org Identifier: ISRCTN59757862.

Correlations between preoperative statin treatment with short- and long-term survival following colorectal cancer surgery: a propensity score-matched national cohort study

IntroductionThe pleiotropic effects of statins have attracted considerable attention in oncological treatment. Several preclinical and epidemiological studies have highlighted their potential anti-tumor properties in patients with colorectal cancer, although results have been conflicting. This study aimed to examine the association between statin exposure before colorectal cancer surgery with long and short-term survival outcomes.MethodsThis retrospective propensity score-adjusted study was conducted on a Danish cohort of patients who underwent elective curative-intended surgery for stage I–III colorectal cancer in 2008–2020, using four national patient databases. The primary and secondary outcomes were overall, 90-day, and disease-free survival. Propensity scores were calculated using all available data to match patients with and without statin exposure in a 1:1 ratio.ResultsFollowing propensity score matching, 7120 patients were included in the primary analysis. The median follow-up time was 5 years. A Cox proportional hazards model showed no statistically significant difference in overall survival between patients with or without statin exposure 365 days before surgery (HR 0.93, 95% CI 0.85–1.02) and no association with 90-day survival (OR 0.91, 95% CI 0.76–1.10). However, a subgroup analysis examining a 90-day exposure before surgery found a statistically significant association with increased overall survival (HR 0.85, 95% CI 0.77–0.93).ConclusionAlthough a subgroup of patients with a preoperative exposure time of 90 days showed statistically significant better overall survival, we found no statistically significant association between statin exposure 1 year before colorectal cancer surgery and overall survival.

Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer.

The fraction of patients who are cancer-free survivors 5 years after curative-intended surgery for colorectal cancer (CRC) is increasing, suggesting that extending surveillance beyond 5 years may be indicated. Here we estimate the incidence of late recurrence, metachronous CRC, and second primary cancers 5-10 years postoperative. All patients resected for UICC stage I-III CRC in Denmark through 2004-2013 were identified. Through individual-level linkage of nationwide health registry data, recurrence status was determined using a validated algorithm. Cancer-free survivors 5 years after surgery, were included. Cumulative incidence functions (CIF) of late recurrence, metachronous CRC, and second primary cancer 5-10 years postoperative were constructed. Subdistribution hazards ratios (sHR) were computed using Fine-Gray regression. Among 8883 patients, 370 developed late recurrence (5-10-year CIF = 4.1%, 95%CI: 3.7%-4.6%), 270 metachronous CRC (5-10-year CIF = 3.0%, 95%CI: 2.7%-3.4%), and 635 a second primary cancer (5-10-year CIF = 7.2%, 95%CI: 6.7%-7.7%). The risk of late recurrence was reduced for patients operated in 2009-2013 compared to 2004-2008 (2.9% vs. 5.6%, sHR = 0.52, 95% CI: 0.42-0.65). The risk of metachronous CRC was likewise reduced from 4.1% to 2.1% (sHR = 0.50, 95%CI: 0.39-0.65). While the risk of second primary cancer did not change between 2009-2013 and 2004-2008 (7.1% vs. 7.1%, sHR = 0.98, 95% CI: 0.84-1.15). Using nation-wide 10-year follow-up data, we document that the incidences of late recurrence and metachronous CRC are low and decreasing from 2004 to 2013. Thus, despite increasing numbers of long-term cancer survivors, the data do not advocate for extending CRC-specific surveillance beyond 5 years.

Recurrence-Free Survival and Disease-Specific Survival in Patients with Pancreatic Neuroendocrine Neoplasms: A Single-Center Retrospective Study of 413 Patients.

The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial. To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3). A single-center retrospective study including consecutive patients over a 20-year period. Multivariate Cox regression analyses were performed to identify risk factors. 413 patients were included, with a mean (SD) age of 62 ± 14 years. In group 1 (n = 51), median (IQR) follow-up was 29 (21-34) months, and tumor size was 1.0 (0.8-1.4) cm. One progressed and had a tumor resection. In group 2 (n = 165), follow-up 59 (31-102) months, median tumor size 2 (1.2-3.4) cm, median Ki-67 index 5 (3-10)%, the 5-year recurrence rate was 21%. Tumor size (p < 0.001), Ki-67 index (p = 0.02), and location in the pancreatic head (p < 0.001) were independent risk factors. In group 3 (n = 197), follow-up 19 (6-46) months, median tumor size 4.2 (2.6-7.0) cm, Ki-67 index 17 (9-64)%, the median disease-specific survival was 22 (6-75) months-99 in NET G1; 54 in NET G2; 14 in NET G3; and 6 months in neuroendocrine carcinomas (NEC). Age (p = 0.029), plasma chromogranin A (p = 0.014), and proliferation, expressed by grade (p = 0.001) and Ki-67 index (p < 0.001), were risk factors. Growth in pNET < 2 cm requiring surgery was observed in 1/51. Tumor size, Ki-67 index, and location in the head were prognostic factors for disease recurrence, while age, plasma chromogranin A, and proliferation predicted mortality in patients with unresectable disease or residual tumors after resection.

Prognostic Significance of Growth Pattern in Predicting Outcome of Opisthorchis viverrini-Associated Distal Cholangiocarcinoma in Thailand

Distal cholangiocarcinoma (dCCA) is a rare type of CCA in Asia, even in Opisthorchis viverrini-prevalent Northeastern Thailand. The clinical ambiguity and imprecision of diagnosis surrounding this malignancy result in high mortality due often to advanced/metastatic disease on presentation. We aim to identify a prognostic factor that can improve the performance stratification and influence the outcome of dCCA patients after curative resection. A total of 79 patients who underwent curative-intended surgery for dCCA was enrolled. Possible risk factors for survival were analyzed with log-rank test, and independent factors with Cox regression model. dCCA patients were staged and classified according to the 8th edition the American Joint Committee on Cancer (AJCC) Staging Manual. Results were then compared with the revised classification employing the prognostic factor identified from multivariate analysis. Multivariate analysis revealed that growth pattern (p < 0.01) and distant metastasis (p = 0.012) were independent factors. Growth patterns comprise intraductal (ID), periductal infiltrating (PI), mass-forming (MF), and mixed types. When dCCA patients were grouped into those having good and poor outcomes (with and without ID components, respectively). The survival outcomes significantly differed among patients with and without ID components, which was better than with the 8th AJCC staging system in our cohort. Furthermore, Chi-square test showed that patterns without ID components (PI, MF, PI + MF) correlated with lymph node and distant metastasis. Therefore, classification of dCCA patients after curative-intended surgical resection based on growth pattern provides additional beneficial information for the prediction of survival in dCCA patients.

Perineural Invasion in Pancreatic Ductal Adenocarcinoma (PDAC): A Saboteur of Curative Intended Therapies?

(1) Background: Perineural invasion (PNI) is a common characteristic of pancreatic ductal adenocarcinoma (PDAC) and is present in most resection margins. We hypothesized that curative pancreatic tumor resection with long-term survival could only be achieved in PNI-negative patients. (2) Material and Methods: A retrospective investigation of PDAC patients who underwent curative-intended surgery during the period 2008 to 2019 was performed at our institution. (3) Results: We identified 571 of 660 (86.5%) resected patients with well-annotated reports and complete datasets. Of those, 531 patients (93%) exhibited tumors with perineural invasion (Pn1), while 40 (7%) were negative for PNI (Pn0). The majority of patients in the Pn1 group presented advanced tumor stage and positive lymph node infiltration. Patients in the Pn0 group showed an improved disease-free and long-term survival compared to the Pn1 group (p < 0.001). Subgroup analysis of all R0-resected patients indicated improved long-term survival and disease-free survival of R0 Pn0 patients when compared to R0 Pn1 patients (p < 0.001). (4) Conclusion: Our study confirmed that Pn0 improves the long-term survival of PDAC-resected cancer patients. Furthermore, PNI significantly challenges the long-term survival of formally curative (R0) resected patients. We provide new insights into the dynamics of PNI in pancreatic cancer patients which are needed to define subgroups of patients for risk stratification and multimodal treatment strategies.

Clinical characteristics and outcome of patients with acute mesenteric ischemia: a retrospective cohort analysis

BackgroundAcute mesenteric ischemia (AMI) is an uncommon, but life-threatening clinical entity due to late diagnosis resulting in irreversible ischemic bowel necrosis. The most common causes of AMI are the embolic occlusion and the acute thrombosis of the mesenteric circulation. Typical treatment is composed of an early revascularization of the mesenteric circulation followed by abdominal surgery for resection of nonviable intestine and restoration of the intestinal continuity, but the mortality rates remain high.MethodsA retrospective cohort analysis was conducted, aiming to evaluate clinical characteristics, performed surgical procedures and outcomes of patients with acute mesenteric ischemia who underwent emergency abdominal surgery at a high volume surgical center in Germany.ResultsOverall, 53 patients were identified with the intraoperatively proven diagnosis of AMI. Overall hospital mortality was with 62% comparable to the literature. Nineteen patients presented with an intraoperatively verified complete and non-reversible intestinal infarction without any angiographic or surgical option for a revascularization of the mesenteric circulation or an option for intestinal resection. From the rest of the patients, 14 underwent intestinal resection of the ischemic area without restoration of intestinal continuity; the other 20 underwent resection with a primary anastomosis to restore intestinal continuity. The mortality rate of these patients with curative-intended surgery remained high (41% of patients died). Pre- and postoperative hyperlactatemia were associated with lower survival of these patients.ConclusionAMI remains a life-threatening abdominal emergency. Therapeutic approaches are highly depended on acting surgeon’s decision, being affected by subjectively rated bowel viability and physical condition of the affected patient. Only selected patients with good bowel viability appear to be suitable for receiving primary anastomosis. The results clearly indicate the need for further research to develop therapeutic approaches for a better management of AMI and to improve outcome of affected patients.

Impact of Lymphadenectomy on the Oncologic Outcome of Patients with Adrenocortical Carcinoma-A Systematic Review and Meta-Analysis.

Simple SummaryThe concept of locoregional lymphadenectomy (LND) in adrenocortical cancer (ACC) has gained interest in recent years, but its definite prognostic and therapeutic significance remains to be established. We undertook a systematic review and meta-analysis to determine the oncologic value of LND in ACC, focusing on overall survival as the primary endpoint. Eleven studies were identified and five were included in the meta-analysis, all of them were retrospective studies. Three studies reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND, whereas studies including patients with stage I–IV ACC (N = 2) did not show a survival benefit of LND. In summary, our results demonstrate an oncologic benefit of LND in patients undergoing curative-intended surgery for at least localized ACC (stage I–III).(1) Background: Locoregional lymphadenectomy (LND) in adrenocortical carcinoma (ACC) may impact oncological outcome, but the findings from individual studies are conflicting. The aim of this systematic review and meta-analysis was to determine the oncological value of LND in ACC by summarizing the available literature. (2) Methods: A systematic search on studies published until December 2020 was performed according to the PRISMA statement. The primary outcome was the impact of lymphadenectomy on overall survival (OS). Two separate meta-analyses were performed for studies including patients with localized ACC (stage I–III) and those including all tumor stages (I–IV). Secondary endpoints included postoperative mortality and length of hospital stay (LOS). (3) Results: 11 publications were identified for inclusion. All studies were retrospective studies, published between 2001–2020, and 5 were included in the meta-analysis. Three studies (N = 807 patients) reported the impact of LND on disease-specific survival in patients with stage I–III ACC and revealed a survival benefit of LND (hazard ratio (HR) = 0.42, 95% confidence interval (95% CI): 0.26–0.68). Based on results of studies including patients with ACC stage I–IV (2 studies, N = 3934 patients), LND was not associated with a survival benefit (HR = 1.00, 95% CI: 0.70–1.42). None of the included studies showed an association between LND and postoperative mortality or LOS. (4) Conclusion: Locoregional lymphadenectomy seems to offer an oncologic benefit in patients undergoing curative-intended surgery for localized ACC (stage I–III).

Postoperative external beam radiotherapy for locoregional control in iodine refractory differentiated thyroid cancer.

BackgroundThe role of postoperative external beam radiotherapy (EBRT) in patients with residual iodine refractory-differentiated thyroid cancer (IR-DTC) is still inconclusive. The aim of this retrospective study was to evaluate locoregional control (LRC) and overall survival (OS), and potential side effects after postoperative EBRT for both microscopic and macroscopic non-radically resected, locally advanced IR-DTC.MethodsBetween 1990 and 2016, 49 patients with locally advanced IR-DTC received EBRT for microscopic (R1; n = 28) or macroscopic (R2; n = 21) locoregional residual disease. For more insight into the added effect of EBRT, we performed an intrapatient sub-analysis in 32 patients who had undergone more than 1 surgical intervention, comparing LRC after primary, curative-intended surgery with LRC after repeated surgery plus EBRT. To estimate LRC and OS, we used Kaplan–Meier curves. From 2007 onward, we prospectively recorded toxicity data in our head and neck cancer database (n = 10).ResultsLRC rates 5 years after EBRT were higher for R1 (84.3%) than for R2 (44.9%) residual disease (P = 0.016). The 5-year OS rate after EBRT was 72.1% for R1 and 33.1% for R2 disease (P = 0.003). In the intrapatient analysis (n = 32), LRC rates were 6.3% 5 years after only initial surgery and 77.9% after repeated surgery with EBRT (P < 0.001). Acute toxicity was limited to grade I and II xerostomia, mucositis, and hoarseness; only one patient developed late grade III dysphagia.ConclusionsPostoperative EBRT is associated with long-lasting LRC and OS with acceptable toxicity in patients with locally advanced IR-DTC, especially in microscopic residual disease.

Factors influencing successful completion of curative-intended surgery for patients with pancreatic malignancy in South Africa

Factors influencing successful completion of curative-intended surgery for patients with pancreatic malignancy in South Africa

Statin use is not associated with improved 30-day survival in patients undergoing surgery for colorectal cancer.

Besides the lipid-lowering properties, statins are thought to have anti-inflammatory effects and it has been shown that statins directly attenuate the inflammatory stress response after surgical trauma. The aim of the study was to examine the association between preoperative statin use and 30-day mortality as well as postoperative complications after curative-intended surgery for colorectal cancer. The study was a Danish nationwide register-based observational study. A total of 29,352 patients undergoing surgery for colorectal cancer between January 1, 2003, and December 31, 2012, were included in the study. At the time of surgery, 5961 were registered as statin users. The outcomes were 30-day mortality and risk of postoperative complications. The adjusted hazard ratio of 30-day mortality was 0.91 (95 CI 0.80-1.04, P = 0.16) among statin users compared with the non-statin group. There was no difference between the two groups regarding the risk of infectious complications (sepsis, anastomotic leakage, pneumonia) (odds ratio 0.95, 95% CI 0.86-1.05, P = 0.31). For other postoperative complications (cardiovascular events, stroke, renal failure, respiratory insufficiency, and thromboembolic events), there was no significant difference between the two groups (odds ratio 0.89, 95% CI 0.78-1.01, P = 0.06). The study did not show an improved 30-day survival after surgery for colorectal cancer in patients treated with statins in the year preceding surgery. No overall association with the risk of postoperative complications was shown.

Multidisciplinary treatment of colorectal liver metastases.

The therapy of patients with colorectal liver metastases (CRLM) has undergone significant changes. Extended survival has been observed to be associated with adoption of hepatic resection and improved chemotherapy. This review summarizes standards, developments and controversies on the management of these patients. Literature search was performed with focus on work published within the last ten years. Patients with CRLM should undergo surgery whenever possible with careful and experienced patient selection as hepatic resection offers the best long-term prognosis. The multidisciplinary approach has markedly evolved and has increased the number of patients in whom curative-intended surgery is possible. Patients with resectable metastases can undergo upfront surgery or may receive perioperative chemotherapy in selected cases, a decision which is under debate and remains individual. Patients with non-resectable metastases that may become resectable upon conversion treatment should receive polychemotherapy with or without local ablative therapy as pretreatment with the main goal of achieving resectability. In patients with synchronous CRLM, the optimal sequence of treatment remains unclear. Depending on the hepatic tumor burden and its dynamics as well as the type and stage of the primary tumor, simultaneous resection or either the sequential "bowel-first" or reversed "liver-first" approach represent suitable options to achieve complete tumor clearance. The improvements in the management of CRLM due to multidisciplinary treatment and novel developments are a great example of successfully pushing the boundaries of cure in metastatic cancer. Surgery aiming at complete tumor clearance represents the central instrument to achieve long-term survival.

Adjunctive role of preoperative liver magnetic resonance imaging added to computed tomography among resected pancreatic cancer patients.

207 Background: Multi-detector computed tomography using pancreatic protocol (pCT) has been a preferred diagnostic imaging modality before resection of the pancreatic ductal adenocarcinoma (PDAC), because an adjunctive role of liver magnetic resonance imaging (MRI) is still unclear. The current study evaluated whether liver MRI added to pCT can help to select proper surgical candidates, and reduce the risk of early recurrence, eventually result in longer survival in resected PDAC patients. Methods: Among 197 PDAC patients who underwent curative-intended surgery, 167 patients who achieved complete resection with no grossly visible tumor were enrolled retrospectively. All patients had no metastatic lesions on pCT and/or MRI, preoperatively. Among them, 102 patients underwent pCT alone (CT group), and 65 patients liver MRI as well as pCT (MRI group). Results: By adding the liver MRI, hepatic metastases were newly discovered in 3 of 58 patients (5.2%) with no hepatic lesions on pCT and in 17 of 53 patients (32.1%) with indeterminate hepatic lesions on pCT. Among 167 patients who achieved R0/R1 resection, the median overall and disease-free survival were 20.1 vs 29.3 months and 8.5 vs 10.0 months in the CT and the MRI group, respectively (p = 0.011 and = 0.012), during median follow-up of 16.4 months. 80 (78.4%) patients in the CT group and 39 (60.0%) in the MRI group experienced recurrence during follow-up. Cumulative initial hepatic recurrence rate was higher in the CT group than in the MRI group (43.7% vs 18.5% at 1yr and 57.4% vs 26.9% at 2yr, p &lt; 0.001), although the other sites recurrence did not differ in both groups. Conclusions: Liver MRI added to pCT has an incremental value in detecting PDAC hepatic metastases. Furthermore, because PDAC patients who underwent resection after liver MRI as well as pCT expect lower rate of hepatic recurrence and better survival than pCT alone, therefore, liver MRI added to pCT is needed to patients who planned curative resection of PDAC.

Tu1939 A Retrospective Single Center Analysis of Survival and Prognostic Factors of Adjuvant Gemcitabine Following Curative-Intended Surgery of Pancreatic Adenocarcinoma

G A A b st ra ct s were de-identified and evaluated by 4 blinded CyPs (3 experienced CyPs, 1 fellow). A modified validated scoring system was used to assess specimen quantity and quality and standardized among all CyPs (Table 1). Final cytologic diagnosis was categorized as: insufficient, benign, atypical, suspicious for malignancy or malignant and final clinical diagnosis as benign or malignant. IOV was calculated using multi-rater kappa (κ) statistics with 95% CI. Bivariate analyses were performed comparing cases with and without uniform agreement followed by logistic regression with backward selection to model the likelihood of uniform agreement. Assuming an overall κ of 0.8 amongst 4 CyPs, prevalence of malignancy of 0.6, and lower limit of 95% CI ≥ 0.7, a sample size of at least 72 cases was determined. RESULTS: 99 cases were included [49% males; mean age 64 yrs] of which 44% presented with weight loss and 28% jaundice. On EUS, mean lesion size was 25 mm, with distribution of lesions being: head/uncinate 56%, neck 8%, body 21% and tail 15%. EUS findings consistent with chronic pancreatitis were noted in 10% of cases. Final cytologic diagnosis revealed malignant diagnosis in 60% of cases, suspicious 4%, atypical 5%, benign 28% and inadequate 3%. IOV for overall final cytologic diagnosis was moderate (κ =0.45) with minimal improvement when combining suspicious + malignant diagnoses (κ=0.54). IOV was slight to fair (κ 0.040.32) for individual parameters (Table 1). Presenting symptom of jaundice (p<0.001), lesion size (p=0.04), number of nucleated/diagnostic cells (p<0.001), degree of GI contamination (p=0.03) and final cytologic (p=0.02) and clinical diagnosis (p=0.003) were significant factors on bivariate analysis (Table 2). On multivariate analysis the predictor for uniform agreement among CyPs was final clinical diagnosis of malignancy [OR 3.99 (CI 1.52-10.49)].CONCLUSIONS: Results of this study demonstrate significant IOV among CyPs for the final cytologic diagnosis and individual quantity and quality measures in the assessment of pancreatic EUSFNA specimens. The final clinical diagnosis of malignancy is the strongest predictor for agreement among CyP. Confirming these results and refinement of EUS-FNA scoring criteria in future multicenter studies is imperative. Table 1: Standardized scoring tool to assess individual EUS-FNA passes and final cytologic diagnosis and IOV of individual parameters

18F-fluorodeoxyglucose positron emission tomography to assess response after radiation therapy in anaplastic thyroid cancer

To assess the interest of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET/CT) to evaluate the tumor response after radiotherapy (RT) in anaplastic thyroid cancer (ATC) patients. 92 patients were treated for ATC at our institution from 1987 to 2012, out of which 64 (70%) received an aggressive multimodal treatment and 28 (30%) a palliative treatment. In the multimodal treatment group, curative-intended surgery, chemotherapy, and RT were delivered in 35 (55%), 59 (92%), and 56 (88%) patients. The maximum standardized uptake value (SUVmax) was determined in tumor (T), nodes (N) and metastases (M) in each available (18)F-FDG PET/CT. The median follow-up was 3.2years. The 1-year actuarial overall survival (OS) was 18% (median: 5.2months) in the entire population and 27% (median: 7months) in the multimodal treatment group. In the multivariate analysis, RT, surgery, and pre-RT chemotherapy independently predicted for OS, with HRs respectively of 0.1, 0.3, and 0.5. Quantification of FDG uptake with SUVmax was assessable in 26 (40%), 19 (30%), and 25 (39%) of (18)F-FDG PET/CT performed initially (prior to any treatment), prior to RT, and after RT, respectively. Mean SUVmax significantly decreased in T (p<0.001), but not in N (p=0.1) and M (p=0.3) during the assessment period, which might be related to the local effect of RT. Comparing pre- and post-RT (18)F-FDG PET/CT, the T mean relative SUVmax decrease was lower (23±54%) in the 4 patients that had a local relapse (LR) as compared with others in the 12 others patients (62±33%; p=0.3). A relative SUVmax decrease inferior to 20% significantly predicted for LR (p=0.02). The prognosis of ATC patients remains dismal despite an aggressive multimodal treatment. Although our results were not significant, (18)F-FDG PET/CT could potentially serve as a surrogate marker of treatment response in ATC.

Intraoperative near-infrared fluorescence imaging of colorectal metastases targeting integrin αvβ3 expression in a syngeneic rat model

AimNear-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin αvβ3-directed NIR fluorescence probe. MethodsLiver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 × 106 CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin αvβ3-directed NIR fluorescence probe. ResultsColorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R2 = 0.92 for the 24 h group, R2 = 0.96 for the 48 h group). ConclusionThese results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin αvβ3 targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.

Surgical treatment of gastric cancer: results in 423 cases

Gastric cancer is the second cause of cancer death worldwide and the first cause in Chile. Management of this pathology is controversial. To report the results on morbidity, mortality, and long-term survival rates of surgical treatment of gastric cancer, and compare them with those reported in the literature. Follow up of 423 patients (aged 16 to 88 years, 271 males) operated for a gastric adenocarcinoma between 1996 and 2002. Patients were staged with the 5th edition of TNM staging system, and the 2nd edition in English of the Japanese Classification of Gastric Cancer. Morbidity was assessed using the classification of the Memorial Kettering Cancer Center group. Kapplan-Meier method was used to assay survival, and Log rank Test to compare long-term survivals. Resectability of the lesions was 70.4%, and 88% of them corresponded to a curative-intended surgery. Seventy percent of patients were in stage TNM IIIA or higher at the moment of surgery. Mortality in curative intended operated patients was 4.2%, and morbidity was 33.7%. Overall five years survival rate was 33%: In the group with curative intended surgery it was 52%. Two years survival rate in the non intended curative group was 3.4%. The reported incidence of complications in our series is similar to that reported in the literature. Five year survival rates, morbidity and mortality were comparable to those reported abroad.

Resultados del tratamiento quirúrgico del cáncer gástrico: Análisis de 423 casos

Gastric cancer is the second cause of cancer death worldwide and the first cause in Chile. Management of this pathology is controversial.To report the results on morbidity, mortality, and long-term survival rates of surgical treatment of gastric cancer, and compare them with those reported in the literature.Follow up of 423 patients (aged 16 to 88 years, 271 males) operated for a gastric adenocarcinoma between 1996 and 2002. Patients were staged with the 5th edition of TNM staging system, and the 2nd edition in English of the Japanese Classification of Gastric Cancer. Morbidity was assessed using the classification of the Memorial Kettering Cancer Center group. Kapplan-Meier method was used to assay survival, and Log rank Test to compare long-term survivals.Resectability of the lesions was 70.4%, and 88% of them corresponded to a curative-intended surgery. Seventy percent of patients were in stage TNM IIIA or higher at the moment of surgery. Mortality in curative intended operated patients was 4.2%, and morbidity was 33.7%. Overall five years survival rate was 33%: In the group with curative intended surgery it was 52%. Two years survival rate in the non intended curative group was 3.4%.The reported incidence of complications in our series is similar to that reported in the literature. Five year survival rates, morbidity and mortality were comparable to those reported abroad.

Postoperative irradiation combined with chemotherapy for high-risk rectal cancer patients

In a prospective open-study we evaluated the combination of radiation therapy and adjuvant 5-FU plus levamisole in controlling Modified Astler-Coller (MAC) B2 or C rectal cancer following a curative-intended surgery. Sixty-four consecutive rectal cancer patients were treated by adjuvant radiation therapy (Linac 8 MV, 50-50.4 Gy to an isocentric pelvis brick volume in 5 fractions per week each of 1.8-2 Gy), and 12 monthly courses of 5-fluorouracil (375 mg/m(2)/day for 5 consecutive days) plus levamisole (50 mg t.i.d. for 3 days). Within a median follow-up period of 36 months, 19 patients (29.6%) experienced relapses. The 3-year-DFS of MAC B2 patients was 82%, compared with 60% in MAC C. Early radiation treatment was not associated with a higher proportion of relapses, while late radiation therapy initiation was associated with a significantly higher proportion of relapses. Early radiation therapy, not later than following the 2nd to 4th course of chemotherapy, is associated with the more acceptable proportion of relapses.

Adjuvant levamisole and fluorouracil in high risk colorectal cancer patients

Adjuvant chemotherapy in colorectal cancer patients is aimed at decreasing the relapse rate of the disease and increasing the disease-free and the overall survival of the patients. In a prospective study we evaluated the efficacy of 5-FU plus levamisole as an aduvant therapy for 153 patients with Dukes' B-2 or C colon or rectal cancer following a curative-intended surgery. Adjuvant chemotherapy was started within 4 to 6 weeks following the operation. Combination of 5-FU 375 mg/m(2)/day was given intravenously over 15-20 min for 5 consecutive days, every month for 1 year. Levamisole 50 mg t.i.d. was administered orally during the first 3 days of each course of chemotherapy. Rectal cancer patients were also irradiated to the tumor bed and pelvic lymphatics. The dose intensities (DI) of 5-FU and levamisole in our study were 432.6 mg/m(2)/w and 103.8 mg/m(2)/w, respectively. Failure analysis in Dukes' B and C patients showed that the rectum accounted for 47.5% of the relapses, of which only 3 cases were in the vicinity of the resected area. Almost half of the failures were observed within the year of adjuvant treatment. The liver was the most common site for first relapse (50%). The 3-year disease-free survival of Dukes' B-2 patients group was 84%, compared with 64% in Dukes' C. The main toxic manifestations were diarrhea, nausea and vomiting, weakness and mucositis. No dose reduction was needed. Our protocol, using lower DI of levamisole yielded similar results with a lower rate of toxicity than other common protocols.