Phase II study of capecitabine plus oxaliplatin (CapOX) as adjuvant chemotherapy for locally advanced rectal cancer (CORONA II).

OBJECTIVE: This multicenter, single-arm phase II study (UMIN000008429) aimed to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapOX) as postoperative adjuvant chemotherapy for patients with locally advanced rectal cancer. METHODS: Patients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin on day 1 and 2000 mg/m2 oral capecitabine on days 1-14, every 3 weeks) after curative surgical resection. The primary endpoint was 3-year relapse-free survival (RFS) rate, and secondary endpoints were 3-year overall survival (OS) rate, treatment compliance, and safety. RESULTS: A total of 40 patients (Stage II, 21; Stage III, 19) were enrolled between September 2012 and November 2015 from seven institutions. Thirty-nine patients (97%) received R0 resection, and 32 patients (84%) received postoperative CapOX therapy. The completion rate of all eight cycles of CapOX therapy was 66%. Relative dose intensities were 87% for oxaliplatin and 84% for capecitabine. At a median follow-up period of 46 months, disease recurrence was observed in nine patients, including three with local recurrence. Three-year RFS and OS rates were 75% (95% CI 57-86%) and 96% (95% CI 80-99%), respectively. Frequencies of Grade ≥ 3 hematological and non-hematologic adverse events were 19% and 38%, respectively. CONCLUSION: CapOX therapy is feasible as adjuvant chemotherapy for locally advanced rectal cancer.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer.

The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.

Importance of the neoadjuvant rectal (NAR) score to the outcome of neoadjuvant chemotherapy alone for locally advanced rectal cancer.

PURPOSE: The neoadjuvant rectal (NAR) score is a promising indicator of survival after preoperative chemoradiotherapy for rectal cancer. However, its effectiveness after neoadjuvant chemotherapy (NAC) alone has not been fully investigated. METHODS: We analyzed data retrospectively on 61 patients with rectal cancer, who received NAC followed by surgical resection between 2010 and 2015, and evaluated the impact of the NAR score on survival. RESULTS: The median NAR score was 14.9. Of the 61 patients, 13, 35, and 13 were classified as having NAR-low (< 8), NAR-intermediate (8-16), and NAR-high (> 16) scores, respectively. The median observation period was 49.0 months. According to the NAR score, the 3-year DFS in the NAR-low group was 100%, which was significantly better than that in the NAR-intermediate (64.8%, p = 0.041), and NAR-high (61.5%, p = 0.018) groups. When the NAR-intermediate and NAR-high groups were investigated as a single high-risk group, the 3-year DFS of the patients who received adjuvant chemotherapy was 88.7%, which was significantly better than that of the patients who did not receive adjuvant chemotherapy (53.3%, p = 0.042). CONCLUSIONS: The NAR score may predict the DFS and could serve as a favorable indicator of adjuvant chemotherapy after NAC alone.

Neoadjuvant CAPOX and bevacizumab alone for locally advanced rectal cancer: long-term results from the N-SOG 03 trial.

BACKGROUND: Neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains an experimental treatment, and the efficacy in terms of long-term outcome has not been fully elucidated. The N-SOG 03 trial examined the safety and efficacy of neoadjuvant CAPOX and bevacizumab (Bev) without radiotherapy in patients with poor-risk LARC. METHODS: Thirty-two patients with MRI-defined LARC received neoadjuvant CAPOX and Bev followed by curative resection between 2010 and 2011. The overall survival (OS), progression-free survival (PFS), and local-relapse rate (LRR) were calculated using the Kaplan-Meier method, and the risk factors were evaluated by multivariate analysis using the Cox proportional hazard models. This trial is registered with UMIN, number 000003507. RESULTS: In the entire cohort, the 5-year OS was 81.3%. Because of disease progression during chemotherapy, 3 patients ultimately did not undergo curative surgery. As a result, 29 patients underwent R0/1 resection. Among these 29 patients, the 5-year OS, PFS, and LRR were 89.7%, 72.4% and 13.9%, respectively. In multivariate analysis, cT4b tumor was an independent poor prognostic factor for OS and LRR, and ypT4b tumor and absence of N down-staging were independent poor prognostic factors for PFS. CONCLUSIONS: Patients with cT4b tumor were not suitable for NAC alone. However, the long-term outcomes of the other patients were satisfactory, and NAC alone might be an option for treatment of LARC. N down-staging was likely to bring favorable PFS, even in patients with cStage III.

Impact of RAS/BRAF mutation status in locally advanced rectal cancer treated with preoperative chemotherapy.

PURPOSE: Our sincere hope is to establish the predictive factors of neoadjuvant chemotherapy (NAC) response and provide patients with greater certainty regarding treatment outcomes. The aim of this study was to assess the response to NAC and survival in patients with locally advanced rectal cancer (LARC) according to their RAS/BRAF mutation status. METHODS: Data on 57 patients with LARC who received NAC between 2009 and 2016 were analyzed retrospectively. The patients were classified into two groups based on their mutation status: wild-type in both RAS and BRAF (WT) or mutant-type in either RAS or BRAF (MT). RESULTS: Twenty-three patients were classified as WT, and the remaining 34 patients were MT. Histological response to NAC was similar in both groups. In responders, the 3-year relapse-free survival (RFS) was better compared with the non-responders (92 and 66%, respectively). In the WT group, the 3-year RFS was 95% which was significantly better than that in the MT group (59%, p = 0.011). The MT group was further subdivided into the following 2 groups by the pathological response; the MT responders (n = 10) and MT non-responders (n = 24). The 3-year RFS was 50% in the MT non-responders, which was significantly worse compared to that in the remaining patients (92%, p = 0.001). CONCLUSION: RAS/BRAF mutations did not affect the response to NAC. However, the RFS was likely to be poor for those in the MT group who did not achieve favorable pathological response. In contrast, the RFS was favorable in the WT group regardless of the pathological response.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer.

Japanese mortality due to colorectal cancer is on the rise, surpassing 49,000 in 2015. Many new treatment methods have been developed during recent decades. The Japanese Society for Cancer of the Colon and Rectum Guidelines 2016 for the treatment of colorectal cancer (JSCCR Guidelines 2016) were prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines were prepared by consensus reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches, and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2016.

The efficacy and safety of CapeOX plus bevacizumab therapy followed by capecitabine plus bevacizumab maintenance therapy in patients with metastatic colorectal cancer: a multi-center, single-arm, phase II study (CCOG-0902).

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of CapeOX plus bevacizumab with a planned oxaliplatin stop-and-go strategy in Japanese patients with metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were treated with 4 cycles of CapeOX plus bevacizumab therapy, followed by capecitabine plus bevacizumab maintenance therapy. Reintroduction of oxaliplatin was scheduled after 8 cycles of maintenance therapy or upon tumor progression. The primary endpoint was progression-free survival (PFS), and secondary end points included overall survival (OS), objective response rate to each treatment, reintroduction rate of oxaliplatin, frequency of peripheral sensory neuropathy (PSN), and safety. RESULTS: The 52 patients who received the protocol treatment were included in the evaluation of efficacy and safety. Median PFS and OS were 12.4 months (95% confidence interval [CI], 10.0-14.8) and 30.6 months (95% CI, 27.6-33.5), respectively. The objective response rates were 55.8% for the initial CapeOX plus bevacizumab therapy, 17.8% for capecitabine plus bevacizumab maintenance therapy, and 31.0% for reintroduced CapeOX plus bevacizumab therapy. The frequency of PSN was 63.5%, including 3.8% of patients with grade 3 PSN. No patients required treatment discontinuation because of PSN during the induction or maintenance therapy. CONCLUSIONS: CapeOX plus bevacizumab therapy with a planned oxaliplatin stop-and-go strategy is a feasible first-line treatment for Japanese patients with mCRC. TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network in 15 March 2010 ( UMIN000006478 ).

Phase II trial of neoadjuvant chemotherapy with S-1 and oxaliplatin plus bevacizumab for colorectal liver metastasis (N-SOG 05 trial).

PURPOSE: This Phase II trial evaluated the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 and oxaliplatin (SOX) plus bevacizumab (Bev) in patients with colorectal liver metastasis (CRLM). METHODS: Patients with initially resectable CRLM received four cycles of SOX plus Bev as NAC. We adopted the R0 resection rate as the primary endpoint, and the threshold R0 resection rate was set at 80%. RESULTS: Between December 2010 and August 2014, 61 patients were enrolled in this study and all started NAC. The completion rate of NAC was 82.0%. Three patients (4.9%) developed severe liver dysfunction caused by NAC and one patient finally decided against resection. Three patients (4.9%) were judged as having progressive disease during or after NAC and did not undergo liver resection. Among 57 patients who underwent liver resection after NAC, three patients were diagnosed with CRLM by pre-treatment imaging modalities and received NAC although a final pathological diagnosis was another malignant disease or benign condition. Finally, 47 of the 54 patients (87.0%) with resected CRLM achieved R0 resection. The pathological complete response rate of the 54 patients was 13.0%, and 31.5% were judged as pathological responders. However, the R0 resection rate of 77.0% in the entire cohort did not meet the endpoint. CONCLUSIONS: NAC with SOX plus Bev has an acceptable toxicity profile and achieved a satisfactory pathological response. However, accuracy of pre-operative diagnoses and liver dysfunction caused by NAC were serious problems. Easy introduction of NAC for initially resectable CRLM should not be performed.

Is There Any Reason to Still Consider Lateral Lymph Node Dissection in Rectal Cancer? Rationale and Technique.

Nodal dissemination in locally advanced rectal cancer occurs mainly in two directions: upward and lateral. Lateral node involvement has been demonstrated; however, lateral lymph node dissection (LLND) is not routinely performed in Western countries and the focus is more on neoadjuvant treatment regimens. The main reasons for this are the high morbidity associated with the operation and the uncertain oncological benefit. There is, however, recent evidence that in selected cases, neoadjuvant treatment combined with total mesorectal excision only might not be sufficient. In this article, the historical developments in the East and the West, the current evidence regarding lateral nodal disease, and the surgical steps in the LLND are discussed.

Modified two-dimensional response as surrogate marker of overall survival in patients with metastatic colorectal cancer.

The identification of surrogate markers for long-term outcomes in patients with metastatic colorectal cancer (mCRC) may help in designing treatment regimens. The aim of this study was to assess whether two-dimensional response (2-DR) can serve as a new surrogate marker for overall survival (OS) in patients with mCRC. The study group consisted of 99 patients with mCRC from two independent cohorts who were treated with oxaliplatin-based chemotherapy plus bevacizumab. Two-dimensional response was defined as an area enclosed by coordinate points, including early tumor shrinkage at 8 weeks, depth of response at nadir, and 20% increase over nadir at progression. Each variable was weighted by its contribution rate to OS. The model was developed and internally validated in the learning cohort, and the performance of this model was externally verified in the validation cohort. Spearman correlation coefficients for 2-DR and OS in the learning and validation cohorts were 0.593 and 0.661, respectively. The C-indexes in predicting OS were 0.724 (95% confidence interval, 0.623-0.815) in the learning cohort and 0.762 (95% confidence interval, 0.651-0.873) in the validation cohort. Overall survival was significantly longer in patients with high 2-DR values than in patients with low 2-DR values in both the learning (37.0 vs. 24.1 months, P < 0.001) and validation (41.2 vs. 20.4 months, P < 0.001) cohorts. In contrast, differences in early tumor shrinkage and depth of response were not statistically significant. Multivariate analyses showed that 2-DR was an independent prognostic factor for OS.

Initial experience of laparoscopic pelvic exenteration and comparison with conventional open surgery.

BACKGROUND: Generalization of laparoscopic pelvic surgery has brought about profound knowledge of the pelvic anatomy and has encouraged expansion of indications for laparoscopic surgery to extended pelvic surgery. Pelvic exenteration (PE) is still a demanding surgical procedure and remains an essential technique for pelvic surgery although minimally invasive and function-preserving surgery is in the mainstream of surgical treatment. However, the techniques of laparoscopic PE (LPE) have been rarely explained nor has its feasibility been fully evaluated. The aim of this study was to describe important technical points and to assess the feasibility of LPE for pelvic malignancies. METHODS: Data on 67 patients with pelvic malignancies, who underwent PE between June 2006 and August 2014, were analyzed retrospectively. LPE has been indicated since 2013. Patients were divided into the LPE group (n = 9) and the conventional open PE (OPE) group (n = 58). RESULTS: Operative time in the LPE and OPE groups was similar (935 vs. 883 min, p = 0.398). Intraoperative blood loss in the LPE group was significantly less than that in the OPE group (830 vs. 2769 ml, p = 0.003). Pathological R0 resection rate was similar in both groups (77.8 vs. 75.9%). Overall incidence of any complication and major complications were much lower in the LPE group (66.7 and 0%) compared to the OPE group (89.7 and 32.8%), although not statistically significant (p = 0.094 and 0.053, respectively). Postoperative hospital stay was significantly shorter in the LPE group than in the OPE group (27 vs. 43 days, p = 0.003). CONCLUSIONS: We confirmed that LPE for pelvic malignancies resulted in less blood loss, a lower complication rate, and shorter postoperative hospital stay compared to OPE. LPE performed by an experienced pelvic surgeon was safe and efficient, and might be a promising option for carefully selected patients.

Growth rate of chemotherapy-naïve lung metastasis from colorectal cancer could be a predictor of early relapse after lung resection.

PURPOSE: The aim of this study was to elucidate a potential risk factor for early relapse after pulmonary metastasectomy of colorectal cancer and to propose an optimal treatment strategy for lung metastasis with an aggressive nature. METHODS: Seventy patients who underwent pulmonary metastasectomy for diachronically measurable pulmonary lesions were retrospectively analyzed. We calculated the tumor doubling time (TDT) as the growth rate of lung metastasis and divided the study population into two groups: Rapid (TDT ≤ 100 days) and Slow (TDT > 100 days). RESULTS: The patients consisted of 47 males and 23 females, with a mean age of 63 years. Forty-two patients had a relapse after pulmonary metastasectomy with a median follow-up duration of 24 months. There was a significant difference in relapse-free survival between the Rapid and Slow groups (p = 0.047). Using a multivariate analysis, no preoperative chemotherapy and a high level of serum carcinoembryonic antigen were proven to be significant risk factors for relapse after metastasectomy. Meanwhile, multivariate analyses among 37 patients without preoperative chemotherapy indicated that TDT was the sole significant factor for relapse-free survival. In addition, eight of nine patients with relapse within 12 months were placed into the Rapid group. CONCLUSIONS: Although this was a preliminary study with a small number of patients, it suggested that lung metastases demonstrating a TDT of 100 days or less have a high risk of early relapse after metastasectomy.

Neoadjuvant treatment for locally advanced rectal cancer: a systematic review.

We reviewed the history and the current status of neoadjuvant treatment for locally advanced rectal cancer (LARC) in Western countries and Japan. The introduction of total mesorectal excision (TME) and preoperative radiotherapy (RT) were treatment revolutions that resulted in improved local control after curative resection for rectal cancer. However, local relapses still occur, even in the era of TME, and remain a cause of recurrence worldwide. The high rate of distant metastasis after curative resection remains a problem. Furthermore, the introduction of newly developed cytotoxic agents into the LARC treatment strategy continues to be an ongoing challenge. Shifting part of an adjuvant chemotherapy (CTx) regimen to the preoperative period is a promising strategy. Currently, various novel methods, such as induction CTx, consolidation CTx, concomitant administration with RT, and neoadjuvant CTx without RT, have been attempted worldwide. Although some strategies have shown favorable short-term outcomes, the long-term efficacy of the treatments needs be evaluated. At the same time, we must investigate clinical and/or molecular biomarkers to predict the therapeutic effects of each treatment, which is the fastest route to providing ideal personalized therapy for patients with LARC.

The feasibility of laparoscopic extended pelvic surgery for rectal cancer.

PURPOSE: The present study aimed to assess the safety and feasibility of laparoscopic extended pelvic surgery for primary or recurrent rectal cancer. METHODS: The data on 77 patients, who underwent extended pelvic surgery between February 2008 and June 2014, were retrospectively analyzed. The patients were divided, based on their treatment history, into an open surgery (OS) group (n = 41) and a laparoscopic surgery (LS) group (n = 36). RESULTS: The operative time in the LS group was significantly longer than that in the OS group (766 vs. 561 min; p < 0.001). In contrast, the LS group was associated with a significantly lower volume of intraoperative blood loss (195 vs. 923 ml; p < 0.001), fluid balance (5.38 vs. 8.23 ml/kg/h; p < 0.001) and rate of complications (40.0 vs. 68.3 %; p = 0.035), and a significantly shorter postoperative hospital stay. The postoperative levels of colloid osmotic pressure and albumin were significantly higher in the LS group. CONCLUSION: The operative time of the LS group was longer than that of the OS group; however, the LS group experienced less blood loss and fewer complications. Moreover, LS was associated with a reduction in intraoperative infusions and a reduced fluid balance, which maintained homeostasis.

The effects of bevacizumab on intestinal anastomotic healing in rabbits.

PURPOSES: The aim of this study was to investigate the effects of the preoperative administration of BV on the healing process of intestinal anastomosis in a rabbit model. METHODS: Twenty male white rabbits were randomly divided into two groups. The control group received saline 1 week before surgery, and the BV group received intravenous BV 1 week before surgery. Each rabbit underwent an enteroenterostomy and a colocolostomy. On postoperative day 7, the bursting pressures of the anastomoses, CD31 and α-smooth muscle actin (α-SMA) staining by immunohistochemistry, the gene expression of α-SMA, and collagen deposition using Picrosirius Red at the site of anastomosis were evaluated. RESULTS: The bursting pressure of small bowel anastomoses was significantly lower in the BV group than in the control group (control 184 ± 10 mmHg vs. BV 140 ± 9 mmHg; p = 0.004). The microvessel counts in the anastomotic tissue were significantly lower in the BV group than in the control group in both the small bowel (p = 0.023) and colon (p = 0.008). The expression of α-SMA, and the degree of collagen deposition decreased in the anastomotic tissue in the BV group compared with the control group. CONCLUSION: The preoperative use of BV may therefore negatively affect the rigidity of intestinal anastomosis.

Clinical Significance of Para-Aortic Lymph Node Dissection for Advanced or Metastatic Colorectal Cancer in the Current Era of Modern Chemotherapy.

BACKGROUND/AIMS: Surgical resection is not generally indicated for para-aortic lymph node (PALN) metastasis from colorectal cancer. However, the clinical significance of PALN dissection (PALND) in the current era of modern chemotherapy has not been fully discussed. METHODS: Between November 2006 and February 2013, 14 patients underwent PALND for colorectal cancer and were proven as having pathological PALN metastasis. The median follow-up was 33.2 months. RESULTS: Primary location was the right-colon in 2 patients, and the left-colon or rectum in 12 patients. The timing of metastasis was metachronous in 5 patients and synchronous in 9 patients. Eleven patients (79%) received perioperative aggressive modern chemotherapy. Neoadjuvant chemotherapy with targeted drugs was introduced in 9 patients (64%) and 6 patients received adjuvant chemotherapy. Recurrence after PALND occurred in 12 patients (86%). The most common site was the lung in 6 patients (43%). The 1- and 3-year disease-free survivals were 39.3 and 7.9%, respectively. The 3-year overall survival were 41.2%. CONCLUSION: The recurrence rate after PALND for strictly selected patients was quite high even in the current era of modern chemotherapy. However, some patients achieved long-term survival or could be cured. Therefore, we should re-evaluate the efficacy of PALND in a larger prospective study.

Role of bevacizumab in neoadjuvant chemotherapy and its influence on microvessel density in rectal cancer.

BACKGROUND: The role of bevacizumab (Bev) in neoadjuvant chemotherapy (NAC) without radiotherapy for rectal cancer has not been fully discussed. The purpose of this study is to assess the clinicopathological benefit of Bev in NAC for rectal cancer and to investigate its influence on microvessel status in cancerous tissue. METHODS: Data on 47 patients with rectal cancer, who received NAC with or without Bev between August 2008 and November 2012, were analyzed retrospectively. The objective response was evaluated using the maximum tumor diameter. Tumor regression grade 3/4 was classified as a pathological response. RESULTS: Thirty-one patients (66 %) received NAC that included Bev and the other 16 patients were treated without Bev. The objective response rate was significantly higher in the Bev group than in the non-Bev group (64.5 vs. 25.0 %, p = 0.015). The rate of pathological response was much higher in the Bev group (41.9 %) than in the non-Bev group (12.5 %), but did not reach significant difference (p = 0.052). Microvessel density (MVD) in the resected cancerous tissue was significantly lower in the Bev group than in the non-Bev group. CONCLUSIONS: We have confirmed that objective and pathological responses were better in patients treated with NAC that included Bev than in those who received NAC without Bev. Additionally, MVD in tumor tissues was inhibited in the patients treated with Bev. To investigate the impact of Bev in NAC on long-term survival, further follow-up is required.

MRI and FDG-PET for assessment of response to neoadjuvant chemotherapy in locally advanced rectal cancer.

BACKGROUND: The purpose of this study was to assess the value of magnetic resonance imaging (MRI) and additional (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC). METHODS: Data on 40 patients with LARC, who were treated with NAC and underwent MRI and FDG-PET/CT before and after NAC, were analyzed retrospectively. Surgery was performed at a median of 6 weeks after NAC and the images were compared with the histological findings. The tumor regression grade 3/4 was classified as a responder. RESULTS: Sixteen patients were pathological responders. Receiver operating characteristic (ROC) analysis revealed that MRI total volume after NAC (MRI-TV2) and ΔMRI-TV had the highest performance to assess responders (area under the ROC curve [AUC] 0.849 and AUC 0.853, respectively). The reduction rate of the maximum standardized uptake value (ΔSUVmax) was also an informative factor (AUC 0.719). There seems no added value of adding FDG-PET/CT to MRI-TV2 and ΔMRI-TV in assessment of NAC responders judging from changes in AUC (AUC of ΔSUVmax and MRI-TV2 was 0.844, and AUC of ΔSUVmax and ΔMRI-TV was 0.846). CONCLUSIONS: MRI-TV2 and ΔMRI-TV were the most accurate factors to assess pathological response to NAC. Although ΔSUVmax by itself was also informative, the addition of FDG-PET/CT to MRI did not improve performance. Patients with LARC who were treated by induction chemotherapy should receive an MRI examination before and after NAC to assess treatment response. A more than 70 % volume reduction shown by MRI volumetry may justify the omission of subsequent radiotherapy.

Postoperative complications following neoadjuvant bevacizumab treatment for advanced colorectal cancer.

PURPOSES: Attempts have been made to use bevacizumab (BEV) in an adjuvant or neoadjuvant setting. However, BEV is known to cause various adverse events, and the safety of neoadjuvant BEV has not yet been fully evaluated. This study assessed the postoperative complications in patients receiving neoadjuvant BEV for colorectal cancer. METHODS: The data for 78 patients with resectable advanced or metastatic colorectal cancer who received neoadjuvant BEV followed by surgical resection were retrospectively analyzed. RESULTS: The median interval between the last BEV dose and surgery was 9 weeks. The most common postoperative complication was pelvic sepsis, which occurred in 11 patients (14 %). A biliary fistula developed in four of 23 patients who underwent liver resection. Anastomotic leakage occurred in six of 24 patients with a colorectal anastomosis, four of whom required re-laparotomy. In a univariate analysis, male gender and a greater intraoperative blood loss were associated with postoperative complications of any grade. Colorectal anastomosis was a risk factor for major complications. In a multivariate analysis, intraoperative blood loss was an independent risk factor for postoperative complications of any grade (HR 6.338; P = 0.003). With regard to major postoperative complications, colorectal primary anastomosis was the only independent predictive risk factor (HR 8.285; P = 0.013). CONCLUSIONS: In patients with colorectal cancer who underwent elective surgery after BEV treatment, the interval between BEV and surgery was not a risk factor for postoperative complications (based on a median interval of 9 weeks). Colorectal primary anastomosis was the only independent risk factor for major postoperative complications.

Cowden syndrome complicated by a gastrointestinal stromal tumor.

To our knowledge, this is the first report of Cowden syndrome complicated by a gastrointestinal stromal tumor (GIST) of the small bowel. A 42-year-old female patient was found to have an abdominal mass that was diagnosed as the cause of anemia and was surgically extracted. The surgical specimen was found to be a GIST. During the same period, the patient underwent an endoscopic examination of the entire gastrointestinal tract. She was also diagnosed as having Cowden syndrome based on gastrointestinal polyps and skin, thyroid and breast lesions. Cowden syndrome is associated with germline mutations in the tumorsuppressor gene PTEN. PTEN expression may be essential to tumor growth and is a predictive biomarker of the prognosis of both diseases. The present report of such a case is expected to further the analysis of Cowden syndrome.