A Prospective, Single-arm, Multicenter Trial of Diverting Stoma Followed by Neoadjuvant Chemotherapy Using mFOLFOX6 for Obstructive Colon Cancer: YCOG 1305 (PROBE Study).

OBJECTIVE: We conducted the first prospective clinical trial of neoadjuvant chemotherapy for patients with obstructive colon cancer. BACKGROUND: Obstructive colorectal cancer is locally advanced colorectal cancer with a poor prognosis. The effect of neoadjuvant chemotherapy for obstructive colon cancer is unclear. METHODS: We conducted a single arm, multicenter trial involving patients from the Yokohama Clinical Oncology Group with obstructive colon cancer. All eligible patients underwent diverting stoma formation before neoadjuvant chemotherapy. Patient received 6 cycles of mFOLFOX6 followed by primary tumor surgery and then 6 cycles of adjuvant chemotherapy. The primary endpoint was the objective response rate of all intended neoadjuvant therapy. The study was registered with the Japanese Clinical Trials Registry as UMIN000013198. RESULTS: Between April 2014, and July 2016, 50 patients were registered, and 46 received neoadjuvant chemotherapy. The objective response rate as the primary endpoint was 67.4%. The most common grade >3 adverse event associated with neoadjuvant chemotherapy was neutropenia (28.3%). Forty-five patients underwent surgical resection of the primary lesion (R0 resection in all cases). Grade >2 surgery-related complications occurred in 7 patients (15.6%). The downstaging rate was 48.9%, and the moderate or greater regression rate was 52.2%; no cases showed pathological complete response. Adjuvant chemotherapy with mFOLFOX6 was performed in 34 patients (75.6%). The 3-year relapse-free and overall survival rates were 76.5% and 95.4%, respectively. CONCLUSION: Neoadjuvant chemotherapy using mFOLFOX6 was feasible and might be a treatment option for patients with obstructive colon cancer. Further large-scale studies are warranted to confirm the present findings.

Relationship between stromal regulatory T cells and the response to neoadjuvant chemotherapy for locally advanced rectal cancer.

BACKGROUND: In addition to the direct power of anticancer drugs, the effectiveness of anticancer therapy depends on the host immune function. The present study investigated whether or not the reduction rate and histological response of preoperative chemotherapy were related to the immune microenvironment surrounding a primary tumor of the rectum. METHODS: Sixty-five patients received preoperative chemotherapy followed by resection from 2012 to 2014; all of these patients were retrospectively analyzed. CD3, CD8, and FoxP3 were immunohistochemically examined as markers for T lymphocytes, cytotoxic T lymphocytes, and regulatory T lymphocytes (Treg), respectively. The correlation between the tumor-infiltrating lymphocyte composition and the tumor reduction rate and histological response to neoadjuvant chemotherapy was investigated. RESULTS: The average tumor reduction rate was 41.5% ± 18.8%. According to RECIST, 47 patients (72.3%) achieved a partial response (PR), and 1 patient (1.5%) achieved a complete response (CR). Eight patients (12.3%) showed a grade 2 histological response, and 2 (3.1%) showed a grade 3 response. A multivariate analysis demonstrated that a low Treg infiltration in stromal cell areas was significantly associated with the achievement of a PR or CR [odds ratio (OR) 7.69; 95% confidence interval (CI) 1.96-33.33; p < 0.01] and a histological grade 2 or 3 response (OR 11.11; 95% CI 1.37-98.04; p = 0.02). CONCLUSION: A low Treg infiltration in the stromal cell areas may be a marker of a good response to neoadjuvant chemotherapy in patients with locally advanced rectal cancer.

Long-term Outcomes of a Randomized Controlled Trial of Single-incision Versus Multi-port Laparoscopic Colectomy for Colon Cancer.

OBJECTIVE: The aim of this study was to evaluate the long-term outcomes that were the secondary endpoints of a RCT of multi-port laparoscopic colectomy (MPC) versus SILC in colon cancer surgery. SUMMARY OF BACKGROUND DATA: The actual long-term outcomes, such as the 5-year RFS, OS, and recurrence patterns after surgery, have not been evaluated by a RCT. METHODS: Patients with histologically proven colon carcinoma located in the cecum, ascending, sigmoid or rectosigmoid colon clinically diagnosed as stage 0-III were eligible for this study. Patients were preoperatively randomized and underwent complete mesocolic excision. The 5-year RFS, OS, and recurrence patterns were analyzed (UMIN-CTR 000007220). RESULTS: Between March 1, 2012, and March 31, 2015, a total of 200 patients were randomly assigned to either the MPC arm (n = 100) or SILC arm (n = 100). The median follow-up for all patients was 61.0 months. An intention-to-treat analysis showed that the 5-year RFS was 91.0% [95% confidence interval (CI) 85.1%-96.9%] in the MPC arm and 88.0% (95% CI 82.1%-93.9%) in the SILC arm (hazard ratio: 1.37; 95% CI 0.58-3.24; P = 0.479). The 5-year OS was 95.0% (95% CI 91.1%-98.9%) in the MPC arm and 93.0% (87.1%-98.9%) in the SILC arm (hazard ratio: 1.39; 95% CI 0.44-4.39; P = 0.568). There were no significant differences in the recurrence patterns between the 2 arms. CONCLUSIONS: Even though the results of the 5-year OS and RFS in this trial were exploratory and underpowered, there were no statistically significant differences between the SILC and MPC arms. SILC may be an acceptable treatment option for select patients with colon cancer.

A multicenter, propensity score-matched cohort study about short-term and long-term outcomes after laparoscopic versus open surgery for locally advanced rectal cancer.

PURPOSE: This study evaluated the results of laparoscopic surgery (LAP) compared to open surgery (OP) for locally advanced mid-to-lower rectal cancer. METHODS: From February 2008 to December 2014, we collected patient data with clinical stage II/III mid-to-lower rectal cancer who underwent resection with LAP or OP at 13 institutions associated with the Yokohama Clinical Oncology Group (YCOG). The short-term outcomes and long-term prognoses associated with LAP and OP were analyzed after adjusting for the patients' backgrounds using propensity score matching. RESULTS: Among 1091 eligible cases, a propensity score matching with six covariates-age, sex, body mass index, American Society of Anesthesiologists physical status category, tumor location, and clinical stage-extracted 237 cases each for the LAP and OP groups, respectively. After matching, there were no differences in background factors between the two groups except for the presence or absence of preoperative treatment. Operative time was significantly longer in the LAP group than that in the OP group (p < 0.001), while the amount of bleeding and the length of postoperative hospital stay were significantly lower in the LAP group than that in the OP group (p < 0.001 and p = 0.001, respectively). There were no significant differences between groups in the incidence of postoperative complications. The 3-year overall survival and relapse-free survival rates were 90.5% and 88.6% and 78.3% and 71.6% in the LAP and OP groups, respectively, which did not differ significantly. CONCLUSIONS: The short-term outcomes and long-term prognoses of LAP in this cohort study indicated that LAP could be a therapeutic option for locally advanced rectal cancer. TRIAL REGISTRATION: UMIN000040406.

Oncological outcomes of lateral lymph node dissection (LLND) for locally advanced rectal cancer: is LLND alone sufficient?

BACKGROUND: Lateral lymph node dissection (LLND) has been considered as the standard treatment strategy for locally advanced lower rectal cancer in Japan. Controversy remains around whether all patients require LLND. This study aims to examine the long-term outcomes of patients in which LLND was performed and clarify the value of LLND. METHOD: Consecutive 458 patients with lower rectal cancer who underwent total mesorectal excision (TME) plus LLND from 1992 to 2012 were included. The long-term outcomes and risk factors for recurrent in patients performed TME + LLND were examined. We assessed the impact of LLND on survival using an estimated therapeutic index. RESULTS: The incidence of LLNM was 15.5%. The 5-year RFS and OS rates of patients with LLNM were 40.9% and 47.7%, while patients without LLNM had a good prognosis. The 5-year local recurrence (LR) rate was 9.2%, and independent risk factors for LR were T4 and LLNM. The LR rate of patients with LLNM was high (22.8%). The LLNM rate of the groups with 0, 1, 2, 3, or 4 risk factors (male, tumor location < 4 cm from anal verge, T4, and MLNM) was 3.8%, 9.2%, 18.1%, and 50.0%. The 5-year OS of the groups was 96.2%, 86.1%, 69.7%, and 48.5%. CONCLUSION: Although patients with locally advanced lower rectal cancer who received LLND had a good prognosis, LLND alone was insufficient to control local recurrence in patients with metastatic lateral nodes.

Long-term results of a randomized study comparing open surgery and laparoscopic surgery in elderly colorectal cancer patients (Eld Lap study).

BACKGROUND: We reported favorable short-term results of laparoscopic surgery in a randomized study comparing open and laparoscopic surgery for elderly patients with colorectal cancer (CRC). The purpose of this study is to clarify the long-term outcomes of the laparoscopic surgery for elderly patients with CRC. METHODS: The inclusion criteria were ≥ 75 years, adenocarcinoma, ≤ T4a, M0 and elective surgery. The patients were randomly allocated to open or laparoscopic surgery according to the tumor location. The survival rates, recurrence and reasons for death were compared. RESULT: One hundred patients (right colon 43, left colon 28, rectum 29) were included in each group. Eight patients who underwent open surgery and 2 patients who underwent laparoscopic surgery were excluded from the analysis because of metastatic diseases and other malignancies found during the operations. One hundred ninety patients (98 open, 98 laparoscopic) were analyzed. There was no difference in the backgrounds excluding more patients with vascular invasion in the laparoscopic rectal cancer. There were no differences in the 5-year overall survival rate (open vs. laparoscopic; 78.9% vs. 82.1%, p = 0.638), 5-year disease-free survival rate (70.5% vs. 62.8%, p = 0.276), 5-year recurrence-free survival rate (76.1% vs. 72.1%, p = 0.419), or 5-year cancer-specific survival rate (86.1% vs. 80.5%, p = 0.208). No differences in survival were detected in the analyses of stage and tumor location. There was no significant difference in the overall recurrence rate or recurrence site. However, distant lymph node metastases and local recurrences were more common after laparoscopic surgery than after open surgery. There was no difference in the cause of death. More than half of the patients died from other diseases in both groups (57.9% vs. 52.6%, p = 0.765). CONCLUSION: Laparoscopic surgery showed similar long-term results compared to open surgery in elderly patients with CRC. Laparoscopic surgery is an effective surgical procedure for elderly patients with CRC.

Hernia incidence following a randomized clinical trial of single-incision versus multi-port laparoscopic colectomy.

BACKGROUND: The short-term results of single-incision laparoscopic colectomy (SILC) showed the safety, feasibility, and effectiveness when performed by skilled laparoscopic surgeons. However, the long-term complications, such as SILC-associated incisional hernia, have not been evaluated. The aim of this study was to determine the incidence of incisional hernia after SILC compared with multi-port laparoscopic colectomy (MPC) for colon cancer. METHODS: From March 2012, to March 2015, a total of 200 patients were enrolled in this study. The patients were randomized to the MPC arm and SILC arm. A total of 200 patients (MPC arm; 100 patients, SILC arm; 100 patients) were therefore analyzed. In all cases the specimen was extracted through the umbilical port, which was extended according to the size of the specimen. A diagnosis of incisional hernia was made either based on a physical examination or computed tomography. RESULTS: The baseline factors were well balanced between the arms. The median follow-up period was 42.4 (range 9.4-70.0) months. Twenty-one patients were diagnosed with incisional hernia, giving an incidence rate of 12.1% in the MPC arm and 9.0% in the SILC arm at 36 months (P = 0.451). In the multivariate analysis, the body mass index (≥ 25 kg/m2) (hazard ratio [HR] 3.03; 95% confidence interval [CI] 1.03-8.92; P = 0.044), umbilical incision (≥ 5.0 cm) (HR 3.22; 95% CI 1.16-8.93; P = 0.025), and history of umbilical hernia (HR 3.16; 95% CI 1.02-9.77; P = 0.045) were shown to be correlated with incisional hernia. CONCLUSIONS: We found no significant difference in the incidence of incisional hernia after SILC arm versus MPC arm with a long-term follow-up. However, this result may be biased because all specimens were harvested through the umbilical port. The study was registered with the Japanese Clinical Trials Registry as UMIN000007220.

Short- and long-term outcomes of laparoscopic versus open lateral lymph node dissection for locally advanced middle/lower rectal cancer using a propensity score-matched analysis.

BACKGROUND: There are few reports on large-scale trials for the long-term outcomes regarding laparoscopic lateral lymph node dissection (LLND). We evaluated the short- and long-term outcomes of laparoscopic versus open LLND for locally advanced middle/lower rectal cancer using a propensity score-matched analysis. METHODS: From January 2005 to December 2016, consecutive clinical stage II to III middle/lower rectal cancer patients who underwent total mesorectal excision (TME) plus LLND were retrospectively collected at three institutions. Laparoscopic LLND was compared with open LLND for the surgical and oncological outcomes, including the long-term survival, using a propensity score-matched analysis. RESULTS: A total of 325 patients were collected. There were 142 patients who underwent open TME plus LLND (open group) and 183 patients who underwent laparoscopic TME plus LLND (laparoscopic group). A total of 93 patients each were matched to each group. Compared to the open group, the laparoscopic group had a significantly longer operative time (327 vs. 377 min; p = 0.002) but significantly less blood loss (540 vs. 50 ml; p < 0.001), fewer Clavian-Dindo grade ≥ 2 postoperative complications (49.5% vs. 34.4%; p = 0.037) and shorter postoperative hospital stay (18 vs. 14 days; p = 0.008). Furthermore, the rate of urinary retention was significantly lower in the laparoscopic group than in the open group (16.1% vs. 6.5%; p = 0.037). The estimated 3-year overall survival, relapse-free survival, and cumulative incidence of local recurrence were 91.4%, 73.1%, and 3.4% in the open group and 90.3%, 74.2%, and 4.3% in the laparoscopic group (p = 0.879, 0.893, 0.999), respectively. CONCLUSIONS: This study showed that laparoscopic LLND had advantages over an open approach, such as less blood loss, fewer postoperative complications, and a shorter postoperative hospital stay, and the oncologic outcomes were similar to the open approach. Laparoscopic LLND could be a viable standard approach to LLND for advanced middle/lower rectal cancer surgery.

The risk factors for incisional hernia after laparoscopic colorectal surgery: a multicenter retrospective study at Yokohama Clinical Oncology Group.

BACKGROUND: Incisional hernia (IH) is a common complication after colorectal surgery. However, the risk factors for incisional hernia after laparoscopic colorectal surgery (LCRS) have not been fully elucidated. This retrospective study analyzed the incidence rate of IH and evaluated the risk factors for IH after LCRS. METHODS: This was a retrospective multi-institution study of 423 colorectal cancer patients conducted between September 2012 and December 2014 in Yokohama Clinical Oncology Group. The diagnosis of IH was based on computed tomography and physical examination findings. The patient-, tumor-, and surgery-related variables were examined by univariate and multivariate analyses. RESULTS: A total of 423 patients were analyzed. The median follow-up period was 48.4 months. IH was observed in 36 patients (8.5%). The 1-year incidence of IH was 5.2%, and the 4-year incidence was 8.5%. A multivariate analysis showed that preoperative umbilical hernia (odds ratio [OR] 5.71; 95% confidence interval [CI] 2.02-16.10; p = 0.001) and a visceral fat area (VFA) ≥ 100 cm2 (OR 2.74; 95% CI 1.08-6.96; p = 0.035) were independent risk factors of IH after LCRS. CONCLUSIONS: The risk factors of IH after LCRS were preoperative umbilical hernia and VFA ≥ 100 cm2. In the case with an umbilical hernia or VFA ≥ 100 performing LCRS, it should likely NOT have a peri-umbilical extraction site and should be considered for an alternate site like a low transverse or Pfannenstiel incision. CLINICAL TRIALS REGISTRATION: The trial was registered with the UMIN Clinical Trials Registry, number 000038707.

Optimal extent of central lymphadenectomy for right-sided colon cancers: is lymphadenectomy beyond the superior mesenteric vein meaningful?

PURPOSE: The objective of the current study was to assess the therapeutic benefit of lymphadenectomy according to the extent of lymphadenectomy. METHODS: Patients undergoing colectomy for right-sided colon cancer were identified. Distribution of lymph node metastases (DLNM) of 1, 2 and 3 were defined as lymph node metastasis (LNM) in the pericolic nodes, the intermediate nodes and the front of the SMV near the origin of the major artery, respectively. The therapeutic index (TI) was calculated based on the frequency of LNM and the 5 year overall survival (OS) rate of patients with LNM. RESULTS: Among 344 patients who met the inclusion criteria, roughly half had LNM (n = 150, 43.7%). While 107 (31.1%) and 30 (8.7%) patients had DLNM1 and DLNM2, respectively, only 13 patients (3.8%) were defined as DLNM3. However, there was no significant difference in 5 year OS by DLNM (DLNM1 71.1%, DLNM2 78.7%, DLNM3 50.4%, p = 0.61). Overall, the TI of lymphadenectomy for D3 area was approximately 1/10 of the TI for D1 (1.9 vs.22.1), given the low frequency of LNM (3.8%) and poor 5 year OS of patients with LNM (50.4%). This trend was consistent irrespective of primary tumor locations. CONCLUSION: The survival benefit from central lymphadenectomy namely D3 was low among patients with right-sided colon cancers.

[Laparoscopic Gastrectomy for Gastric Cancer with Adachi Type â ¥ Vascular Anomaly-A Case Report].

We report a case of laparoscopic gastrectomy for gastric cancer with an anomalous celiac trunk categorized as Type Ⅵ- Group 24 in the Adachi classification. Upper gastrointestinal endoscopy in an 81-year-old male revealed a shallow depressed lesion in the middle of the gastric body. Close examination led to diagnosis of cT1bN0M0, cStage Ⅰ gastric cancer, and laparoscopic distal gastrectomy was planned. Contrast-enhanced CT revealed no anomalous bifurcation of the hepatic artery, but the common hepatic artery ran on the dorsal side of the portal vein, branching from the superior mesenteric artery. Therefore, an Adachi Type Ⅵ-Group 24 celiac trunk anomaly was diagnosed. During surgery, the common hepatic artery could not be confirmed in guiding suprapancreatic lymph node dissection, and the portal vein was exposed. Anterior to the portal vein, nerves that are usually around the common hepatic artery continuously ran toward the hepatoduodenal ligament instead. Suprapancreatic lymph nodes were dissected, with the portal vein considered as the common hepatic artery. Adachi Type Ⅵ is a rare anomaly with an incidence of about 2%. Preoperative diagnosis enables safe and appropriate lymph node dissection.

A prospective, single-arm, multicenter trial of neoadjuvant chemotherapy with mFOLFOX6 plus panitumumab without radiotherapy for locally advanced rectal cancer.

PURPOSE: The present study evaluated the safety and efficacy of neoadjuvant chemotherapy with modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus panitumumab in clinical stage III rectal cancer with KRAS wild-type. METHODS: We conducted a prospective multicenter phase II trial. KRAS wild-type clinical stage III rectal cancer patients were enrolled. Patients received 6 cycles of mFOLFOX6 with 6 mg/kg panitumumab as neoadjuvant chemotherapy. The primary outcome was the response rate (RR) defined by RECIST. Lateral lymph node dissection (LLDN) was performed when patients had a locally advanced tumor < 9 cm from the anal margin. RESULTS: A total of 50 patients were enrolled. Twelve (24.0%) experienced grade 3-4 adverse events during neoadjuvant chemotherapy. The RR was 88.0% (complete response 2.0%, partial response 86.0%), which met the primary outcome. All patients underwent laparoscopic surgery and achieved R0 resection. Seven patients underwent resection of other adjacent organs, and 43 underwent LLND. Twelve patients (24.0%) experienced grade 3-4 postoperative complications, and 4 (8.0%) had pathological complete response (pCR). Thirteen patients (26.0%) had lymph node metastasis. Forty-five patients (90.0%) received postoperative adjuvant chemotherapy. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 79.0% and 93.7%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy of mFOLFOX6 plus panitumumab without radiotherapy resulted in a low pCR rate but a high PR rate, low local recurrence rate, and good long-term outcome, suggesting that this treatment strategy may be a viable option for patients unable or unwilling to receive radiotherapy. The trial was registered with the UMIN Clinical Trials Registry, number 000006039.

Risk factors of chemotherapy-induced nausea and vomiting in patients with metastatic colorectal cancer: a prospective cohort study (YCOG1301).

PURPOSE: Although the effectiveness of antiemetic therapy for colorectal cancer chemotherapy has improved with further drug development, some patients still suffer from chemotherapy-induced nausea and vomiting (CINV) even with only 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. The present study investigated the risk factors of CINV in patients who received chemotherapy for colorectal cancer and clarified which patients need additional neurokinin 1 receptor antagonist. METHODS: Patients with colorectal cancer receiving moderate-emetic-risk chemotherapy (MEC) were enrolled in this prospective single-arm study with intravenous palonosetron 0.75 mg and dexamethasone 9.9 mg before chemotherapy and with paroral dexamethasone 8 mg on days 2 and 3. The primary endpoint was the complete response (CR) rate for delayed-phase CINV. RESULTS: A total of 179 patients were eligible for this study. The delayed CR rate was 84.9% (152/179). There were no significant differences in any risk factors, but women with a low body mass index (BMI) (a combination of "female sex" and "BMI < 20") showed a significantly lower rate of CC (complete control) (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.17-1.13; p = 0.039), and young patients with a low BMI (combination of "age < 65" and "BMI < 20") showed a significantly lower rate of CR (OR = 0.34, 95% CI = 0.13-0.88; p = 0.022) than the other patients. CONCLUSIONS: This study failed to identify any single risk factors associated with delayed CINV in patients who received chemotherapy for advanced colorectal cancer. However, combinations of "thin and women" or "young and thin patients" might be possible predictive conditions, thus, candidates for NK1 receptor antagonist administration in MEC. Further investigations are required to develop criteria for the supplementation of NK1 receptor antagonist.

Indocyanine green fluorescence imaging to reduce the risk of anastomotic leakage in laparoscopic low anterior resection for rectal cancer: a propensity score-matched cohort study.

BACKGROUND: Recent studies have shown the potential benefit of indocyanine green fluorescence imaging (ICG-FI) in lowering the anastomotic leakage (AL) rates by changing the surgical plan. The aim of this study was to evaluate the effect of ICG-FI on the AL rates in laparoscopic low anterior resection (LAR) for rectal cancer. METHODS: From September 2014 to December 2017, data from patients who underwent laparoscopic LAR for rectal cancer were collected and analyzed. The primary endpoint was the AL rate within 30 days after surgery. The incidence of AL in patients who underwent ICG (ICG-FI group) was compared with that in patients who did not undergo ICG (non-ICG-FI group) using propensity score matching. RESULTS: Data from 550 patients were collected from 3 institutions. A total of 211 patients were matched in both groups by the propensity score. ICG-FI shifted the point of the proximal colon transection line toward the oral side in 12 patients (5.7%). The AL rates of Clavien-Dindo (CD) grade ≥ II and ≥ III were 10.4% (22/211) and 9.5% (20/211) in the non-ICG-FI group and 4.7% (10/211) and 2.8% (6/211) in the ICG-FI group, respectively. ICG-FI significantly reduced the AL rate of CD grade ≥ II and ≥ III (odds ratio (OR) 0.427; 95% confidence interval (CI) 0.197-0.926; p = 0.042 and OR 0.280; CI 0.110-0.711; p = 0.007, respectively). The rate of reoperation was significantly lower (OR 0.192; CI 0.042-0.889; p = 0.036) and the postoperative hospital stay significantly shorter (mean difference 2.62 days; CI 0.96-4.28; p = 0.002) in the ICG-FI group than in the non-ICG-FI group. CONCLUSIONS: ICG-FI was associated with significantly lower odds of AL in laparoscopic LAR for rectal cancer. CLINICAL TRIAL: The study was registered with the Japanese Clinical Trials Registry as UMIN000032654.

Efficacy and safety of enoxaparin for preventing venous thromboembolic events after laparoscopic colorectal cancer surgery: a randomized-controlled trial (YCOG 1404).

PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal cancer (LAC) in Japanese patients. METHODS: The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24-36 h after surgery and continued until discharge (Enoxaparin group; n = 61), or IPC alone (IPC group; n = 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up. RESULTS: The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((p = 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event. CONCLUSIONS: It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC. The UMIN Clinical Trials Registry number was UMIN000018633.

The risk factors for urinary dysfunction after autonomic nerve-preserving rectal cancer surgery: a multicenter retrospective study at Yokohama Clinical Oncology Group (YCOG1307).

AIM: The aim of this retrospective study was to evaluate the frequency and risk factors of urinary dysfunction after autonomic nerve-preserving surgery for rectal cancer. METHODS: This was a retrospective multiinstitution study of 1002 rectal cancer patients conducted between January 2008 and December 2012 in Yokohama Clinical Oncology Group. Patients who had preoperative urinary dysfunction or had not undergone autonomic nerve preservation surgery were excluded. Urinary dysfunction was defined as that with a Clavien-Dindo classification grade ≥ 2. Patient-, tumor-, and surgery-related variables were examined by univariate and multivariate analyses. RESULTS: A total of 887 patients were analyzed. Postoperative urinary dysfunction was observed in 77 patients (8.8%). A multivariate logistic analysis showed that a tumor location in lower rectum (odds ratio [OR] 2.16; 95% confidence interval [CI] 1.15-3.71; p = 0.02), tumor diameter ≥ 40 mm (OR 2.07; 95% CI 1.19-4.44; p < 0.01), operation time ≥ 240 min (OR 2.07; 95% CI 1.19-4.44; p < 0.01), blood loss ≥ 300 ml (OR 2.35; 95% CI 1.12-3.84; p = 0.02), and diabetes (OR 3.26; 95% CI 1.80-5.89; p < 0.01) were independent risk factors of urinary dysfunction. The incidence of urinary dysfunction exceeded 20% in patients with 3 preoperative predictors (tumor location, tumor diameter, diabetes). CONCLUSIONS: This result demonstrated that high-risk patients with more than two risk factors should be informed of the risk of urinary dysfunction. TRIAL REGISTRATION: UMIN000033688.

Long-term outcome and prognostic factors for patients with para-aortic lymph node dissection in left-sided colorectal cancer.

BACKGROUND: Para-aortic lymph node (PALN) metastasis of colorectal cancer is rare, and the treatment strategy for PALN metastasis (PALNM) is not established in contrast to liver or lung metastases. We sought to evaluate the survival outcomes and prognostic factors among patients undergoing surgery combined with extended lymphadenectomy for PALNM from left-sided colorectal cancer. METHODS: From 1992 to 2012, 322 patients who underwent PALN dissection (PALND) synchronously with primary resection, among 1819 left-sided colorectal surgical cases, were retrospectively examined. We investigated the overall survival (OS) and prognostic factors for patients with PALNM. RESULTS: Of the 322 patients, 62 (19.3%) were histologically confirmed to have PALNM. The 5-year OS in patients with and without PALNM was 19.5% and 67.0% (p < 0.001), respectively. Among patients with PALNM, on the multivariable analysis, the positive resection margin (hazard ratio (HR) 3.61; 95% confidence interval (CI) 1.85-7.06), undifferentiated histological type ((por/muc/sig), HR 4.51; 95% CI, 2.22-9.19), ≥ 4 PALNMs (HR 3.34; 95% CI 1.53-7.31), and preoperative CEA ≥ 10 ng/mL (HR 2.1; 95% CI 1.11-4.27) were significant prognostic factors. Among R0 resected cases, the 5-year OS of the 17 cases with ≤ 3 PALNM and well/moderately differentiated adenocarcinoma was 54.2%, which was comparable to that of patients undergoing PALND and diagnosed with stage IIIC (49.6%). CONCLUSION: Patients with PALNM of colorectal cancer had a poor prognosis. However, curative resection, ≤ 3 PALNM, and well/moderately differentiated histology type were associated with the long-term survival.

Randomized controlled trial to evaluate laparoscopic versus open surgery in transverse and descending colon cancer patients.

BACKGROUND: The safety and efficacy of laparoscopic surgery for transverse and descending colon cancer remain controversial. This study aimed to evaluate the short- and long-term outcomes of this procedure. METHODS: We conducted a single-institutional randomized controlled trial. Patients with transverse or descending colon cancer were randomly allocated to receive laparoscopic surgery (LAC) or conventional open surgery (OC). The primary endpoint was the overall complication rate between the two groups. The secondary endpoints were the length of the postoperative hospital stay, the health-related quality of life (HRQOL) score (at 1, 6, and 12 months after surgery), the 5-year relapse-free survival (RFS), and the 5-year overall survival (OS). RESULTS: Between August 2008 and October 2012, a total of 66 patients were enrolled (33 in the LAC group and 33 in the OC group). The patient characteristics showed no significant differences between the two groups. The complication rates (≥ grade 3) were 6.1% in the LAC group and 12.1% in the OC group (p = 0.392). The length of postoperative stay was not significantly different between the two groups. Regarding the HRQOL, the physical functioning, role physical, bodily pain, social functioning, mental health, and role component summary at 1 month after surgery and the social functioning and mental health at 6 months after surgery were better in the LAC group than in the OC group. The 5-year RFS and OS rates were similar between the LAC and OC groups (RFS 90.5% and 87.3%, respectively, p = 0.752; OS 93.3% and 100.0%, respectively, p = 0.543). CONCLUSIONS: The short- and long-term outcomes of laparoscopic surgery for transverse and descending colon cancer are almost equal to those of open surgery. Laparoscopic resection is a better choice than open surgery for managing this cancer with regard to the short- and mid-term QOL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01861691 .

Short-term and long-term results of a randomized study comparing high tie and low tie inferior mesenteric artery ligation in laparoscopic rectal anterior resection: subanalysis of the HTLT (High tie vs. low tie) study.

BACKGROUND: In rectal anterior resection, a clear consensus regarding the optimal level of inferior mesenteric artery (IMA) ligation does not exist because of a lack of randomized trials. We conducted a randomized trial to determine if the IMA should be tied at the origin (high tie, HT) or distal to the left colic artery (low tie, LT) (HTLT study). This study is a subanalysis of HTLT study for laparoscopic surgery. METHODS: All candidates were randomly divided into the HT or LT groups. The lymph node dissection around the origin of the IMA was performed in the LT group. The stratified factor was the approach (open or laparoscopy). Evaluation parameters were operative factors, short-term and long-term results. In the present study, laparoscopic surgeries were examined as subgroup analysis. RESULTS: From June 2006 to September 2012, 331 patients were registered. Two hundred and fifteen patients (107 for HT: 108 for LT) underwent laparoscopic surgeries. There was no difference between the groups in background. The incidence of anastomotic leakage (HT: LT %) showed no significant differences for grade 2 or higher (11.2:9.3), and grade 3 or higher (2.8:4.6). There were no differences in operative time (200:205 min), blood loss (15:15 ml), number of dissected lymph nodes (22:20), and postoperative hospital stay (10:10 days). The incidence of bowel obstruction in HT was significant (3.7 vs. 0%, p = 0.043). There were no significant differences in overall survival (5-year: 91.3 vs. 90.2%, p = 0.850) and disease-free survival (5-year: 83.2 vs. 78.0%, p = 0.525). There were no differences in the first recurrent site and death reason between both groups. The risk factors for leakage were being male and an anastomotic level in a multivariate analysis by logistic regression. CONCLUSION: The IMA ligation level was unrelated to anastomotic leakage. No significant difference was detected in long-term results between HT and LT.

Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial.

OBJECTIVE: The aim of the study was to confirm the noninferiority of mesorectal excision (ME) alone to ME with lateral lymph node dissection (LLND) in terms of efficacy. BACKGROUND: Lateral pelvic lymph node metastasis is occasionally found in clinical stage II or III lower rectal cancer, and ME with LLND is the standard procedure in Japan. ME alone, however, is the international standard surgical procedure for rectal cancer. METHODS: Eligibility criteria included histologically proven rectal cancer at clinical stage II/III; main lesion located in the rectum, with the lower margin below the peritoneal reflection; no lateral pelvic lymph node enlargement; Peformance Status of 0 or 1; and age 20 to 75 years. Patients were intraoperatively allocated to undergo ME with LLND or ME alone in a randomized manner. The primary endpoint was relapse-free survival, with a noninferiority margin for the hazard ratio of 1.34. Secondary endpoints included overall survival and local-recurrence-free survival. Analysis was by intention to treat. RESULTS: In total, 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n = 350) groups. The 5-year relapse-free survival in the ME with LLND and ME alone groups were 73.4% and 73.3%, respectively (hazard ratio: 1.07, 90.9% confidence interval 0.84-1.36), with a 1-sided P value for noninferiority of 0.0547. The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in the ME with LLND and ME alone groups, respectively (P = 0.024). CONCLUSIONS: The noninferiority of ME alone to ME with LLND was not confirmed in the intent-to-treat analysis. ME with LLND had a lower local recurrence, especially in the lateral pelvis, compared to ME alone.