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.

Tumor-infiltrating CD45RO(+) memory cells are associated with a favorable prognosis breast cancer.

BACKGROUND: CD45RO is a marker for memory lymphocytes. Whether CD45RO(+) tumor-infiltrating lymphocytes (TILs) prevent breast cancer recurrence is unclear. METHODS: In the present study, we evaluated CD45RO expression in TILs as a predictor of prognosis in 98 patients with breast cancer who underwent radical surgery without neoadjuvant chemotherapy. Patients were classified as CD45RO(+)/TILs(High) or CD45RO(+)/TILs(Low) based on median immunohistochemistry levels. RESULTS: CD45RO(+)/TILs(High) were associated with smaller tumor size. The CD45RO(+)/TILs(High) group also had significantly fewer metastatic lymph nodes (P = 0.0082) and fewer peritumoral lymphatic invasions (P = 0.0284). The CD45RO(+)/TILs(High) group enjoyed longer recurrence-free survival (P = 0.0453) but not cancer-specific survival (P = 0.0640) in univariate analysis. CONCLUSIONS: These results suggested that CD45RO(+) effector cells may both help eradicate local tumors and prevent metastases to the lymphatic systems in breast cancer patients. High ratio of CD45RO expressing TILs was associated with recurrence-free survival improvement and a trend toward cancer-specific survival improvement in breast cancer patients.

Implication of duration of clinical presentation on tumor progression and short-term recurrence in patients with early breast cancer.

Breast cancer growth is dependent on time and it may be of utmost importance to take into consideration the duration of clinical symptoms in order to predict which patients are at high risk for disease recurrence. The aim of this study was to determine the association between duration of clinical symptoms and disease recurrence in patients with breast cancer. A total of 139 consecutive patients with primary breast cancer who underwent a radical breast operation were retrospectively investigated and the association between recurrence and the duration of symptoms was investigated. The duration of clinical signs was defined as the time from the onset of symptoms to the date of surgery. The breast cancer cases were divided into two groups on the basis of symptom duration (≤6 and >6 months). The mean duration of symptoms was 191.0±242.6 days. Of the 139 cases, 36 (25.9%) had a duration of symptoms of >6 months. In the univariate analysis, a statistically significant association with long symptom duration was observed for disease recurrence. Of the 139 patients, 6 (4.3%) developed recurrent disease. The univariate analysis revealed that long duration of symptoms and nuclear grade were significantly associated with recurrence. In conclusion, our results indicated that breast cancer progression is dependent on time. A long duration of symptoms (>6 months) may be considered as an indicator of tumor progression and a strong prognostic factor in breast cancer patients.

Impact of vascular invasion of a primary tumor as a strong risk factor for disease recurrence in patients with node-positive breast cancer.

The presence of lymph node metastasis is considered to be the most significant indicator of prognosis. However, in some cases with node-positive breast cancer, cancer cell dissemination is localized to the lymphatic systems. It is, therefore, important to develop selection criteria for strong adjuvant therapy in patients with node-positive breast cancer. This study was undertaken to evaluate the presence of vascular invasion that may reflect systemic disease as a predictor of disease recurrence in node-positive breast cancer. We retrospectively evaluated the cases of 134 consecutive female patients with breast cancer with lymph node metastasis who underwent radical breast operations. We examined the relationship between recurrence and clinicopathological factors, particularly vascular invasion. The presence of vascular invasion was found to be significant in a univariate analysis. The presence of vascular invasion was the independent risk factor in a multivariate analysis. Among the 66 patients without vascular invasion, four (6.1%) had disease recurrence. On the other hand, among the 68 patients with vascular invasion, 15 (22.1%) had a recurrence. It is interesting to note that despite the presence of lymph node metastasis, the group without vascular invasion had few patients with distant metastases. Our results suggest that the presence of vascular invasion could be an indicator of high biological aggressiveness and may be a strong prognostic factor for node-positive breast cancer.

Significance of lymphatic invasion combined with size of primary tumor for predicting sentinel lymph node metastasis in patients with breast cancer.

BACKGROUND/AIM: Lymphatic invasion (ly) may mainly reflect the selective affinity of breast cancer cells for lymph nodes. We conducted the present study to investigate whether the presence of lymphatic invasion is a predictor of sentinel lymph node (SLN) metastasis in clinically node-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated the cases of 202 consecutive female patients with clinically node-negative primary breast cancer who underwent a radical breast operation with SLN biopsy. We examined the relationship between SLN metastasis and the significance of clinicopathological factors, including lymphatic invasion. RESULTS: Among the 202 patients, 49 (24.3%) had SLN metastasis. The univariate and multivariate analyses revealed that the size of the tumor and lymphatic invasion were independent risk factors for SLN metastasis. Among the 96 patients who were ly-negative and had a tumor size of less than 20 mm, only 5 (5.2%) had 1-2 metastases within the SLN. Among the 34 patients who were ly-negative and had a tumor size of less than 10 mm, there were no patients with SLN metastasis. CONCLUSION: Our results suggest that the presence of lymphatic invasion combined with the size of the primary cancer could be considered a strong risk factor for SLN metastasis in clinically node-negative breast cancer, and patients with a tumor size of less than 20 mm and clinically node-negative breast cancer may avoid axillary lymph node dissection after SLN biopsy. There is also a possibility that SLN biopsy could be unnecessary for patients with clinically node-negative breast cancer who are ly-negative and have a tumor size of less than 10 mm.

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.

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.

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.

Arteriovenous malformation detected by small bowel endoscopy.

Gastrointestinal bleeding that originates in the small intestine is often difficult to diagnose. When successful diagnosis reveals a lesion that can be localized preoperatively, the laparoscopic approach is an appropriate and beneficial treatment modality for small bowel resection. A 69-year-old man presented with a 6-month history of gastrointestinal bleeding and symptomatic transfusion-dependent anemia. Upper and lower endoscopy were normal. Double-balloon endoscopy established the source of the bleeding as a 0.5-cm polypoid mass appearing as a submucosal tumor with redness and pulsation in the lower ileum, suggesting a vascular lesion. Laparoscopic small bowel resection was successful in removing the mass in the ileum. Histological evaluation of the mass revealed an arteriovenous malformation. Preoperative small bowel endoscopy can be useful for diagnosing the cause and localization of arteriovenous malformation in the small intestine.

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.

Extracapsular invasion of sentinel lymph nodes is not associated with disease recurrence in breast cancer.

The purpose of this study was to evaluate the presence of extracapsular invasion (ECI) in positive sentinel lymph nodes (SLNs) as a predictor of disease recurrence in breast cancer. SLN biopsy was performed on 318 breasts of 316 breast cancer patients, of which 50 (15.7%) had positive SLNs. Six (12.0%) of these 50 cases had disease recurrence. The clinicopathologic features of these cases were reviewed. The ECI at SLNs was not significantly associated with disease recurrence. The recurrence-free interval by Kaplan-Meier curves did not differ significantly among patients with and without ECI at SLNs. On the other hand, metastasis at non-SLNs was observed in 12 cases (24.0%) among the 50 cases with positive SLNs, and in the non-SLN metastasis group there were 7 patients with ECI at non-SLNs. Three of 7 cases with ECI at non-SLNs had disease recurrence and none of those 5 without ECI at non-SLNs had disease recurrence. Our current study suggests that the presence of ECI at metastatic SLNs is not associated with recurrent disease in breast cancer. Our results also imply that patients with ECI at positive non-SLNs have a high risk of disease recurrence.

Serum albumin and prealbumin do not predict recurrence in patients with breast cancer.

BACKGROUND: We have previously reported that prealbumin and albumin may be sensitive indicators of the risk of recurrent disease in colorectal cancer; however, the relationship between preoperative prealbumin and cancer survival has not been fully-elucidated. The purpose of this study was to examine the relationship between preoperative nutritional conditions, including prealbumin and albumin concentrations, and the risk of recurrence in cases with breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven patients who underwent breast surgery were analyzed in this study. The detection limit of the prealbumin assay was 22 mg/dl; patients were divided in analytical groups of <22 mg/dl and ≥22 mg/dl. The detection limit of the albumin assay was 4.0 g/dl; patients were divided in analytical groups of <4.0 g/dl and ≥4.0 g/dl. The clinical features of these cases were reviewed according to prealbumin and albumin levels, and statistical analysis was performed. RESULTS: Among 157 cases in this study, five (3.2%) had disease recurrence. Out of the eligible cases, 38 (24.2%) had decreased serum prealbumin and 19 (12.1%) had decreased serum albumin preoperatively. No statistically significant association of the preoperative prealbumin level was found with the clinicopathological variables. The only statistically significant association found for preoperative albumin level was age; age was higher in patients with low albumin levels. In short, we were unable to establish a connection between preoperative prealbumin or albumin and various clinical features, including recurrence, lymph node metastasis and tumor size. CONCLUSION: Prealbumin and albumin may be sensitive indicators of disturbances in protein metabolism, and reflect inflammation activity and malnutrition. However, our results suggest that evaluation of serum prealbumin and albumin are not useful for predicting disease aggressiveness or recurrence in breast cancer.

Effect of long interval between hyperthermochemoradiation therapy and surgery for rectal cancer on apoptosis, proliferation and tumor response.

Neoadjuvant chemoradiotherapy is commonly used to improve the local control and resectability of locally advanced rectal cancer, with surgery performed after an interval of a number of weeks. We have been conducting a clinical trial of preoperative chemoradiotherapy in combination with regional hyperthermia (hyperthermo-chemoradiation therapy; HCRT) for locally advanced rectal cancer. In the current study we assessed the effect of a longer (>10 weeks) interval after neoadjuvant HCRT on pathological response, oncological outcome and especially on apoptosis, proliferation and p53 expression in patients with rectal cancer. Forty-eight patients with proven rectal adenocarcinoma who underwent HCRT followed by surgery were identified for inclusion in this study. Patients were divided into two groups according to the interval between HCRT and surgery, ≤ 10 weeks (short-interval group) and >10 weeks (long-interval group). Patients in the long-interval group had a significantly higher rate of pathological complete response (pCR) (43.5% vs. 16.0%) than patients of the short-interval group. Patients of the long-interval group had a significantly higher rate of down-staging of T-stage (78.3% vs. 36.0%) and relatively higher rate of that of N-stage (52.2% vs. 36.0%) than patients of the short-interval group. Furthermore, apoptosis in the long-interval group was relatively higher compared to that of the short-interval group, without a significant difference in the Ki-67 proliferative index and expression of p53 in the primary tumor. In conclusion, we demonstrated that a longer interval after HCRT (>10 weeks) seemed to result in a better chance of a pCR, a result confirmed by the trends in tumor response markers, including apoptosis, proliferation and p53 expression.

Vascular invasion, but not lymphatic invasion, of the primary tumor is a strong prognostic factor in patients with colorectal cancer.

BACKGROUND: We previously showed that the presence of vascular invasion, but not lymphatic invasion, was a strong prognostic factor for breast cancer. Lymphatic invasion may represent mainly the selective affinity of cancer cells for lymph nodes. The present study was undertaken to evaluate the presence of vascular invasion that may reflect systemic disease as a predictor of disease recurrence in colorectal cancer, separate from lymphatic invasion of the primary tumor. PATIENTS AND METHODS: We retrospectively evaluated the cases of 177 consecutive patients with primary colorectal cancer who underwent colorectal resection. We examined the relationship between recurrence and the prognostic significance of clinicopathological factors, particularly lymphatic and vascular invasion. RESULTS: The presence of vascular invasion (v) was significant, while that of lymphatic invasion (ly) was not significant in univariate analysis. The presence of vascular invasion was an independent prognostic factor in multivariate analysis. Among the 60 patients in the ly-/v- group, one (1.7%) had disease recurrence, and among the 33 patients in the ly+/v- group, one (3.0%) had disease recurrence. On the other hand, among the 71 patients in the ly+/v+ group, 16 patients (22.5%) suffered recurrence, and among the 13 patients in the ly-/v+ group, four (30.8%) suffered recurrence. It is interesting to note that despite the presence of lymphatic invasion, the group without vascular invasion (ly+/v-) had a few patients with distant metastases, a result which is similar to that of the ly-/v- group. CONCLUSION: The presence of vascular invasion, but not lymphatic invasion, could be an indicator of high biological aggressiveness and may be a strong prognostic factor for colorectal cancer.

A rare case of anterior chest wall schwannoma masquerading as a breast tumor.

A schwannoma is a tumor that develops on peripheral nerves or spinal roots. Although any part of the body can be affected, the breast is a quite unusual site for schwannomas. We report herein a case of schwannoma presenting as a breast tumor. In the current case, the tumor showed both clinically and mammographically as a well-defined breast mass. Of interest, sonographically, the well-defined mass appeared to be located in subcutaneous tissue, not in breast parenchyma, and this finding was confirmed histopathologically. These findings indicate the possibility that a schwannoma arising from subcutaneous breast tissue can show exophytic growth to the breast and appear as a breast tumor. In other words, our case implies the possible presence of a "pseudo" breast schwannoma.