Clinical and Radiological Discrimination of Solitary Pulmonary Lesions in Colorectal Cancer Patients.

OBJECTIVES: The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. METHODS: Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. RESULTS: All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). CONCLUSIONS: The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.

Control of primary lesions using resection or radiotherapy can improve the prognosis of metastatic colorectal cancer patients.

BACKGROUND: Control of the primary lesions in metastatic colorectal cancer (mCRC) is still controversial. For rectal cancer patients, not only resection but also irradiation is expected to provide palliative effects. We investigated the effects of resection and irradiation of primary lesions (local control) on the prognosis of mCRC patients. PATIENTS: Forty-seven patients with mCRC at our institute were examined, with 34 in the local controlled group and 13 in the uncontrolled group. RESULTS: The median survival time (MST) of the local controlled and uncontrolled groups were 2.90 and 1.39 years (P = 0.028). Cox proportional hazard regression analysis showed that local control was an independent prognostic factor (P < 0.05). The patients who underwent primary lesion resection had significantly longer MST (2.90 vs. 1.39 years, P = 0.032) than those in the uncontrolled group. In rectal cancer patients, the patients who underwent irradiation to control the primary lesions had a significantly longer MST than the uncontrolled patient group (1.97 vs. 1.39 years, P = 0.019). CONCLUSIONS: Local control of primary lesions may improve the prognosis in mCRC patients. In rectal cancer patients with metastasis, not only resection but also irradiation of the primary lesions may be a useful therapeutic strategy. J. Surg. Oncol. 2016;114:75-79. © 2016 Wiley Periodicals, Inc.

KPNA2 over-expression is a potential marker of prognosis and therapeutic sensitivity in colorectal cancer patients.

BACKGROUND: Karyopherin α 2 (KPNA2) is a member of the Karyopherin α family and has recently been reported to play an important role in tumor progression. The aim of the current study was to elucidate the clinicopathological significance of KPNA2 over-expression in colorectal cancer (CRC). PATIENTS AND METHODS: KPNA2 expression was evaluated by immunohistochemistry in 122 surgically resected CRC and 13 biopsy specimens obtained at colonoscopy during screening for preoperative hyperthermochemoradiation therapy (HCRT). The association between KPNA2 expression and clinicopathological features and preoperative HCRT efficacy were examined. RESULTS: The high and low KNPA2 expression groups were comprised of 91 (74.6%) and 31 CRC patients, respectively. A significant association was observed between high expression and lymphatic invasion (P = 0.0245). KPNA2 high expression group had decreased overall survival (P = 0.00374). Multivariate analysis demonstrated high KPNA2 expression was independently associated with poor prognosis. Histological examinations revealed 11 (84.6%) and 2 (15.4%) of cases were KPNA2 positive and negative, respectively. Pathological complete response (pCR) was observed in 9.1% of KPNA2-positive cases and 100% of KPNA2-negative cases. CONCLUSION: High KPNA2 expression was found to be associated with poor prognosis and resistance to HCRT.

Prognostic value of extracapsular invasion of axillary lymph nodes combined with peritumoral vascular invasion in patients with breast cancer.

BACKGROUND: Extracapsular invasion (ECI) of metastatic axillary lymph nodes has been associated with aggressive nodal disease but its prognostic role in breast cancer is unclear. The present study evaluated nodal ECI as a predictor of breast cancer recurrence. METHODS: We evaluated 154 women with histologically proven node-positive breast cancer who were diagnosed with invasive ductal carcinoma, and investigated the relationships between ECI and recurrences and other clinicopathological factors, particularly vascular invasion and the number of lymph node metastases. RESULTS: The presence of ECI at positive nodes was significantly associated with the number of positive nodes, and with disease recurrence and survival in univariate (but not multivariate) analysis. Interestingly, all ECI(+) patients with distant metastases in our series had peritumoral vascular invasion (PVI), which may have reflected systemic disease; ECI with PVI of the primary tumor strongly predicted recurrent disease and shorter survival. CONCLUSION: ECI of axillary metastases combined with PVI indicates high tumor aggressiveness. Patients with ECI and PVI may be considered for stronger adjuvant therapies because of their high risk for distant recurrences.

Feasibility of Reduced Port Laparoscopic Colectomy for Colon Cancer.

BACKGROUND/AIMS: Reduced port laparoscopic surgery has recently emerged as a method to improve the cosmetic results of conventional laparoscopic surgery. We reported our technique of reduced port laparoscopic colectomy using 3-port and short-time outcomes. METHODOLOGY: Between 2005 and 2012, we performed 161 reduced port laparoscopic colectomies using the 3-port technique. Data analyzed in-cluded age, gender, body mass index (BMI), duration of surgery, number of harvested lymph nodes, and duration of hospital stay. RESULTS: All of the cases were successfully performed using the 3-port procedure. The median durations of surgery and postoperative hospital stay were 140 mm (range 75-463 mm) and 9 days (range 5-38 days), respectively. No mortality was associated with this technique. CONCLUSION: Reduced port laparoscopic colectomy is feasible and may have advantages over conventional laparoscopic colectomy.

Clinicopathological Features of Second Primary Colorectal Cancer Incidentally Identified by 18F-FDG-PET.

As positron emission tomography using F18-fluorodeoxyglucose (FDG-PET) is becoming a common imaging modality the number of colorectal cancers incidentally detected by FDG-PET is expected to increase. In this study, we investigated the clinicopathological features of 15 cases of second primary colorectal cancer incidentally detected by PET during other cancer evaluation in patients who underwent surgery. We also discussed the significance of FDG-PET in evaluating cancer status. None of the patients had undergone FDG-PET for suspected colorectal disease; 6 were being evaluated by FDG-PET for lung cancer, 5 for nasopharyngeal or laryngeal cancer, 3 for gastrointestinal cancer, and 1 for uterine cancer. The average tumor size was 36.1 ± 14.4 mm (range, 25-70 mm) and the mean maximum standardized uptake value (SUVmax) was 11.9 ± 6.0 (range, 3.0-29.6). Although 4 cases (26.7%) had distant metastasis, 3 (20%) were Tis or T1 cancer, 3 (20%) were T2 cancer. Of the 15 cases, 6 (40%) could have been underwent laparoscopic surgery. Our study found that asymptomatic cases of colorectal cancer can be detected by FDG-PET during evaluation for other cancer. Therefore, in some cases, FDG-PET is useful for detecting second primary colorectal cancer at a relatively early and curable stage.

Outlet Obstruction of Temporary Loop Diverting Ileostomy.

Stoma formation is commonly performed in operations to treat carcinoma, inflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP). In this study, we report several cases of stomal outlet obstruction and investigate the clinical features of cases of outlet obstruction in patients who underwent diverting loop ileostomy. Sixty-one patients with IBD, FAP or rectal cancer who required diverting loop ileostomy were identified for inclusion in this study. We defined outlet obstruction as a small bowel obstruction at the opening of the ileostomy following surgery. All cases of outlet obstruction were diagnosed by computed tomography. In the univariate analysis the type of diagnosis, type of operation, age, and white blood cell count were the factors significantly associated with outlet obstruction following ileostomy, and outlet obstruction was considered to have a connection with restorative proctocolectomy. In conclusion, we found that adhesion and twisting of the ileostomy were the causes of outlet obstruction. For temporary diversion, simple rotation of the ileostomy should be recommended, especially in restorative proctocolectomy. Additional study is required to explore other risk factors of outlet obstruction.

C-reactive protein level as a possible predictor for early postoperative ileus following elective surgery for colorectal cancer.

BACKGROUND/AIMS: Inflammatory reactions are par- tially responsible for postoperative ileus (POI). Serum C-reactive protein (CRP) is an acknowledged marker of inflammation. In this study the CRP response with respect to POI in elective colorectal surgery was exam- ined to define the role of serum CRP as an early predic- tor of POI. METHODOLOGY: Three hundred eighty-three patients who underwent elective colorectal resection were identified for inclusion in this study. We defined early POI as that occurring within 30 days following the surgery. Thirty-five patients with POI were com- pared to a subgroup of 348 patients with an unevent- ful postoperative course, and the correlation between postoperative serum CRP levels and POI in colorectal surgery was investigated. RESULTS: In the univariate analysis, length of operation, surgical blood loss, and serum CRP were factors significantly associated with POI following colorectal surgery; however, these fac- tors lost their significance on multivariate analysis. CONCLUSION: Our results suggest that an increase in CRP levels alone is not a predictor for POI following surgery for colorectal surgery. Although inflammatory responses are known to contribute to the ileus, ad- ditional study is required to identify risk factors that would be more useful for prediction of POI.

Extracapsular lymph node involvement is associated with colorectal liver metastases and impact outcome after hepatectomy for colorectal metastases.

BACKGROUND: Hepatic resection of metastatic colorectal cancer (CRC) has become the treatment of choice for patients after resection of the primary CRC. However, some patients do not benefit from immediate resection because of rapidly progressive disease. The aim of this study was to examine the prognostic value of extracapsular invasion (ECI) of lymph node (LN) metastasis of CRC with liver metastases following liver resection. METHODS: All patients who underwent resection for CRC with liver metastases between 1995 and 2011 were reviewed. All of those with metastasis from primary CRC were included in this study. Preoperative, intraoperative, and postoperative data, including primary tumor pathology results, were retrospectively reviewed. All resected LNs from primary CRC were re-examined to assess ECI. Associations between clinicopathologic factors, survival, and the nodal findings were evaluated. RESULTS: ECI was identified in 47 (48%) patients. ECI was correlated with the number of positive LNs (p = 0.0022), timing of liver metastasis (p = 0.0238), and number of liver metastases (p = 0.0001). Univariate analysis indicated that the number of positive LNs (p = 0.0014), ECI (p = 0.0203), and adjuvant chemotherapy (p = 0.0423) were significant prognostic factors. Patients with ECI had a significantly worse survival (p = 0.0024) after liver resection than patients with LN-negative and ECI-negative groups. CONCLUSIONS: In patients with hepatic CRC metastases, ECI in regional LNs reflects a particularly aggressive behavior, such as a greater number of liver metastases. In CRC patients with liver metastases, ECI in regional LNs might be correlated with poor prognosis following liver resection.

FDG-PET/CT of schwannomas arising in the brachial plexus mimicking lymph node metastasis: report of two cases.

BACKGROUND: Schwannoma is a tumor that develops on peripheral nerves or spinal roots. Although any part of the body can be affected, axillar and supraclavicular lesions are unusual for schwannoma. We report two cases of schwannoma arising in the brachial plexus, which were detected by 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT). CASE 1: A 75-year-old Japanese woman showed high FDG accumulation in a subclavicular or axillary lesion found by FDG-PET/CT. Axillar-subclavicular lymph node metastasis was suspected and surgical excision was performed. Histological evaluation revealed schwannoma. CASE 2: A 75-year-old Japanese woman was diagnosed with suspected primary lung cancer with brain metastases. She showed high FDG uptake at a subclavicular or axillary lesion found by FDG-PET/CT. Surgical excision was performed to arrive at a definitive diagnosis. The mass was located at the trunk of the brachial plexus and was identified as a schwannoma. CONCLUSION: Although schwannoma within an axillar or subclavicular lesion is relatively rare, brachial plexus schwannoma should be considered in the diagnosis of masses detected by FDG-PET/CT.

Adenoma of the nipple projecting out of the nipple: curative resection without excision of the nipple.

BACKGROUND: Adenoma of the nipple is a rare breast tumor that is often mistaken clinically for Paget's disease and misinterpreted pathologically as invasive ductal carcinoma. CASE REPORT: We report herein a distinctive case of adenoma of the nipple projecting out of the nipple. In the current case, we were able to perform curative resection through a periareolar incision similar to a microdochectomy without excision of the nipple. The diagnosis of adenoma of the nipple was confirmed histopathologically. CONCLUSION: Although the tumor was found on top of the nipple, curative tumor resection without excision of the nipple was possible and the nipple was completely preserved. Adenoma of the nipple is a benign tumor, and thus the diagnosis of adenoma of the nipple must be confirmed so that unnecessary surgery can be avoided.

Addition of Bevacizumab to First-Line Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND/AIMS: We evaluated the efficacy and safety of bevacizumab for metastatic colorectal cancer patients. METHODOLOGY: All unresectable metastatic colorectal cancer patients who began receiving bevacizumab at participating facilities from 2006 to 2011 were retrospectively analyze to determine the safety and efficacy. The primary end points were Progression Free Survival (PFS) and Overall Survival (OS). The secondary end points were adverse events. RESULTS: A total of 101 patients were enrolled in the study. The primary tumor site was the colon in 53 patients and the rectum in 48 patients. The most common metastatic sites were the liver (63.4%), lung (31%), and peritoneum (10%). In first-line therapy, 76 (75.2%) patients received the FOLFOX regimen. Among these patients, 33 (43.4%) patients received FOLFOX alone, and 43 (56.6%) received FOLFOX plus bevacizumab. The addition of bevacizumab to first-line chemotherapy was associated with increases in median PFS (12.5 vs. 6.0 months; P = .00001) and median OS (24.0 vs. 16.0 months; P = 0.0221). The risks of adverse events were not significantly increased with the addition of bevacizumab. CONCLUSIONS: The addition of bevacizumab to first-line therapy in CRC patients provided clinically significant patient benefit, including statistically significant improvement in OS and a favorable tolerability profile.

MUTYH-associated colorectal cancer and adenomatous polyposis.

MUTYH-associated polyposis (MAP) was first described in 2002. MUTYH is a component of a base excision repair system that protects the genomic information from oxidative damage. When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as the APC and/or the KRAS genes, via G to T transversion. MAP is a hereditary colorectal cancer syndrome inherited in an autosomal-recessive fashion. The clinical features of MAP include the presence of 10-100 adenomatous polyps in the colon, and early onset of colorectal cancer. Ethnic and geographical differences in the pattern of the MUTYH gene mutations have been suggested. In Caucasian patients, c.536A>G (Y179C) and c.1187G>A (G396D) mutations are frequently detected. In the Asian population, Y179C and G396D are uncommon, whereas other variants are suggested to be the major causes of MAP. We herein review the literature on MUTYH-associated colorectal cancer and adenomatous polyposis.

Elevated C-reactive protein is associated with the tumor depth of invasion but not with disease recurrence in stage II and III colorectal cancer.

BACKGROUND/AIMS: We previously demonstrated that elevated serum C-reactive protein (CRP) level is associated with depth of tumor invasion in operable colorectal cancer. There is also increasing evidence to show that raised CRP concentration is associated with poor survival in patients with colorectal cancer. The purpose of this study was to investigate the correlation between preoperative CRP concentrations and short-term disease recurrence in cases with stage II and III colorectal cancer. METHODOLOGY: Of the 224 cases with resected colorectal cancer, 55 patients with TNM stage II and 50 with stage III were analyzed in this study. The clinical features were reviewed according to the CRP level, and statistical analysis was performed. In cases with stage II and III, 11 and 6 of which had elevated serum CRP (>=10mg/L), respectively. Recurrence-free interval was defined as the interval from surgery to the time disease recurrence was diagnosed. Among the cases with stage II and III colorectal cancer, 4 and 10 had recurrent disease. RESULTS: Among various clinicopathological characteristics, depth of tumor invasion was independently associated with preoperative elevation of CRP in stage II and III colorectal cancer in multivariate subgroup analysis. However, recurrence-free interval by Kaplan-Meier curves did not differ significantly among patients with preoperative CRP concentrations. CONCLUSIONS: Our results suggest that elevated serum CRP level is associated with depth of tumor, but not with recurrent disease in stage II and III colorectal cancer.

The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor.

BACKGROUND/AIMS: Although tumors metastasize to lymph nodes via the lymphatics, the importance of vascular endothelial growth factor-C (VEGF-C) expression in mediating the process has not been well elucidated. We investigated the correlation between VEGF-C expression and lymphatic vessel density (LVD) and node metastasis in cases with gastric cancer and gastrointestinal stromal tumor (GIST). METHODOLOGY: Immunohistochemistry, VEGF-C expression and LVD were performed in 41 patients with gastric cancer invading the muscularis propria and 19 patients with GIST. The clinicopathological features of these cases were compared. RESULTS: In gastric cancer, VEGF-C expression was significantly associated with tumor LVD and lymph node metastasis. In GIST, none of these patients had lymph node metastasis and VEGF-C expression was not detected. The LVD was significantly higher in the cases with gastric cancer than in those with GIST. In gastric cancer, LVD was increased more in patients with positive lymph nodes than in those with negative lymph nodes. CONCLUSIONS: These results indicate that the expression of VEGF-C is associated with tumor LVD and lymph node metastasis, suggesting that VEGF-C plays a critical role in node metastasis via lymphangiogenesis. The clinical observation that GIST rarely metastasizes to the lymph nodes may depend on the lack of VEGF-C expression.

Synchronous colorectal liver metastasis in patients without node metastasis: possibility of localized liver metastasis.

BACKGROUND/AIMS: The liver is the most common distant site of metastasis from colorectal cancer and is often the only organ affected. We hypothesized that whether distant disease is localized in the liver or is a more systemic disease, may be important in the prognosis of patients with synchronous liver metastasis. The purpose of this study was to investigate the possibility of localized liver metastasis in cases with colorectal synchronous liver metastasis and without lymph node involvement. METHODOLOGY: Three hundred and twenty-five consecutive patients who underwent colorectal resection were identified for inclusion in this study, of which 24 cases with synchronous liver metastasis were detected. Of these, 11 who underwent curative simultaneous surgical resection of primary tumor and liver metastases were analyzed in this study. The clinical and pathological features of these cases were reviewed. RESULTS: Of the 11 patients with synchronous liver metastasis from colorectal cancer, 4 had disease recurrence, but none of those without regional node involvement had disease recurrence. In the multivariate analysis, only regional node metastases were significantly associated with disease recurrence. Recurrence-free interval by Kaplan-Meier curves differed significantly among patients with positive regional nodes. CONCLUSIONS: Our results imply that synchronous liver metastasis without regional lymph node metastasis is localized disease.

Bowline knot of a monofilament suture eliminates C-loop formation in intracorporeal ligation.

We describe how we developed a new method of tying an intracorporeal suture of monofilament material using a bowline knot, which eliminates the troublesome C-loop formation for winding the thread on the rod. The winding-forceps point to the site of suturing, and the needle end of the thread is placed under the rod of the forceps during the knot tying. This position allows for easy winding of the line even when the forceps-angle is as narrow as 10° because the winding-forceps and suture line are in parallel. This method resolves the problems of C-loop formation with a narrow forceps-angle. Thus, our bowline method of knot-tying provides an easy, secure, and rapid intracorporeal ligation requiring a short learning curve, as an alternative to the conventional C-loop method.

Associated expression of α2,3sialylated type 2 chain structures with lymph node metastasis in distal colorectal cancer.

PURPOSE: One of the typical modifications on the surface of cancer cells is sialylation of terminal carbohydrates. The expression of several types of sialylation of glycoconjugates was investigated in colorectal cancer. METHODS: The cancer tissue specimens obtained from 65 colorectal cancer patients were stained with sialic acid-binding lectins from Maackia amurensis (MAM), Sambucus sieboldiana (SSA), Maackia amurensis agglutinin (MAA) and monoclonal antibodies, and compared with their clinicopathological features. RESULTS: Cancer tissue specimens from 44.6% of patients had positive staining with MAM, which recognized α2,3sialylated type 2 chain (NeuAcα2,3Galß1,4GlcNAcßR) structures, but normal colorectal mucosa showed only weak staining with MAM was observed. More lymph node metastases and lymphatic invasion were seen in patients with positive staining with MAM (P < 0.01), while not with other lectins or antibodies that recognized sialylated glycoconjugates or sialyl Lewis-related antigens. The five-year survival rate of patients with MAM-positive staining was significantly lower than that with MAM-negative staining when including T0-1 cases, but there was no difference in cases with T2-4. There was no difference in the patients' survival rates when the tissues were stained with MAA, SSA or PNA lectins. CONCLUSION: α2,3Sialylated type 2 chain structures were predominantly expressed in colorectal tissues associated with the malignant transformation, in particular, with lymphatic spread of distal colorectal adenocarcinomas.

Clinicopathological significance of decreased galectin-3 expression and the long-term prognosis in patients with breast cancer.

PURPOSE: Galectin-3 expression is modulated in cancer cells, and that finding has led to the recognition of galectin-3 as a diagnostic or prognostic marker for various cancers, including breast cancer. This study investigated the correlation between galectin-3 expression and the clinicopathological features in patients with breast cancer, in order to determine the relevance and role of galectin-3 in breast cancer progression. METHODS: Galectin-3 expression was investigated immunohistochemically in 116 patients with breast cancer, and a statistical analysis was performed. RESULTS: Galectin-3 expression in breast cancer was significantly associated with tumor vascular invasion. However, galectin-3 expression was not associated with Ki-67 expression, which reflects tumor proliferation. Disease-free survival and long-term overall survival were significantly shorter for patients with reduced galectin-3 expression. CONCLUSIONS: This study demonstrated that the galectin-3 expression was associated with tumor vascular invasion and metastasis, suggesting that galectin-3 plays a critical role in tumor progression via an invasive mechanism but not via proliferation in breast cancer. Furthermore, reduced expression of galectin-3 is useful for predicting a long-term poor prognosis in patients with breast cancer.

Phase II trial of chemotherapy plus bevacizumab as second-line therapy for patients with metastatic colorectal cancer that progressed on bevacizumab with chemotherapy: the Gunma Clinical Oncology Group (GCOG) trial 001 SILK study.

OBJECTIVES: BRiTE and ARIES (observational cohort studies) provided valuable information on continued use of bevacizumab (BV) beyond progression (BBP). This trial evaluates the efficacy and safety of BBP for patients with metastatic colorectal cancer that progressed on first-line chemotherapy. METHODS: A total of 39 patients received FOLFIRI + BV (after FOLFOX + BV) or FOLFOX + BV (after FOLFIRI + BV) as protocol treatment. The primary endpoint was the response rate. Secondary endpoints were overall survival (OS), total survival from initiation of first-line treatment (TS), progression-free survival (PFS), and safety. RESULTS: All 39 treated patients were evaluated for toxic effects. Two patients did not meet all of the eligibility criteria and were excluded from efficacy analyses. The response rate was 16.2%. The disease control rate was 76%. The median PFS was 150 days (range 117-224). The median OS was 417 days (range 233-813). The median TS was 988 days (range 600-1,268). Grade 3/4 adverse events (% of patients) related to treatment were neutropenia (33%), fatigue (23%), and hypertension (18%). CONCLUSIONS: This is the first report to show the effect of BBP in patients who had progressive disease on first-line treatment including BV confirmed by RECIST criteria. This analysis suggests the possibility of prolonged survival with continued use of BV.