The clinical significance of elastic lamina invasion in patients with pStage II colorectal cancer: a notable prognostic indicator.

BACKGROUND: Some colorectal cancers (CRCs) are clinically diagnosed as cT4a with　serosal invasion (SI). However, the cT4a is most often underdiagnosed pathologically as pT3 without SI by hematoxylin-eosin (H&E) staining alone. Using Elastica van Gieson (EVG) staining, some pT3 tumors invade the elastic lamina (EL), which extends just below the serosal layer. Recently, EL invasion (ELI) has been described as a poor prognostic factor for disease-free survival (DFS) and overall survival (OS) in patients with pStage II CRC. However, its clinicopathological significance remains unclear due to the limited number of studies and poor understanding of ELI. OBJECTIVE: This study investigated the association between the ELI and patient prognosis. METHODS: After 1982, pathological diagnosis was routinely performed using H&E and EVG staining methods, and long-term follow up was performed until 2016. All clinicopathological features including ELI were prospectively registered into our computer and 569 patients with pStage II CRC were collected from the database. Based on the ELI status, pT3 was divided into three pathological categories: pT3ELI - was defined as pT3a, pT3ELI + as pT3b and unidentified EL (pT3EL -) as pT3u. RESULTS: Using H&E staining alone, gross cT4a was most often pathologically underdiagnosed as pT3 (93.8%) and very rarely as pT4a, resulting in a large diagnostic discrepancy. Using EVG staining, 60.7% of the cT4a tumors were diagnosed as pT3b. The 10-year DFS and OS rates were similar for pT3a and pT3u patients. However, the 10-year DFS and OS rates of pT3b patients were significantly lower than those of pT3a patients (75.6% vs. 95.6%, p < 0.0001 and 58.4% vs. 70.6%, p = 0.0024, respectively) but did not differ from those of pT4a patients (70.6%, p = 0.5799 and 52.0%, p = 0.1116, respectively). Multivariate analysis revealed that the ELI was the strongest independent risk factor for recurrence and CRC-specific death (p < 0.0001). CONCLUSIONS: A better understanding of the ELI allows us to reconsider the diagnostic discrepancy of serosal invasion, i.e., pT3b should be considered pT4a. The ELI-based subclassification of pT3 is expected to be incorporated into the TNM staging system in the future. The ELI is a notable prognostic indicator in patients with pStage II CRC.

A prospective study of XELOX plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer (KSCC 0902).

BACKGROUND: This study was designed to evaluate the efficacy and safety of XELOX plus bevacizumab in a Japanese metastatic colorectal cancer population that included elderly patients. METHODS: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated metastatic colorectal cancer, presence of measurable lesions, age ≥ 20 years; Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELOX (130 mg/m(2) oxaliplatin on day 1 plus 1,000 mg/m(2) capecitabine b.i.d. on days 1-14) every 3 weeks. The primary endpoint was confirmed objective response rate. RESULTS: The study included 47 patients (male/female 30/17; median age 69 years; age range 38-81 years with 10 patients ≥ 75 years; PS 0/1/2, 40/5/2) enrolled between May 2010 and March 2011. Responses were assessed in 46 eligible patients. The objective response rate was 52.2 % (95 % confidence interval [CI] 37.0-67.1). The median progression-free survival and overall survival were 10.0 months (95 % CI 7.8-12.3) and 34.6 months (95 % CI 19.9-not estimable), respectively. Frequently encountered grade 3 and 4 adverse events in this study were aspartate aminotransferase elevation (23.4 %), alanine aminotransferase elevation (21.3 %), anorexia (12.8 %), neutropenia (10.6 %), fatigue (8.5 %) and anemia (6.4 %). Grade 3 or 4 peripheral neuropathy was not observed. CONCLUSION: First-line treatment with XELOX plus bevacizumab showed a promising response rate and an acceptable tolerability profile in the clinical practice of Japanese metastatic colorectal cancer patients that included elderly patients. REGISTRY: UMIN-CTR, ID number: UMIN000003915, URL:https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004706&language=E.

Primary breast peripheral T-cell lymphoma not otherwise specified: report of a case.

Malignant lymphomas of the breast are rare and primary breast lymphoma comprises <0.5 % of breast malignancies, within which T-cell lymphomas are an even rarer subset. We report a case of primary breast peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). Histology of the biopsied specimen revealed CD2(+), CD3(+), CD4(+), CD5(-), CD7(+), CD8(-), CD20(-), CD25(-), CD30(+), CD56(-), bcl-2(-), EBV-ISH(-), TIA-I(-), and ATLA negative. The patient was treated with six cycles of the CHOP regimen and died 17 months after the diagnosis was made, despite complete remission after conventional chemotherapy. To our knowledge, only 18 cases of primary peripheral T-cell lymphoma of the breast and just one previous case of primary PTCL-NOS of the breast have been reported in Japan.

T1 squamous cell carcinoma of the esophagus: long-term outcomes and prognostic factors after esophagectomy.

BACKGROUND: Mucosal (T1a) and submucosal (T1b) squamous cell carcinoma of the esophagus (ESCC) have often been analyzed together and are staged as the same category in the UICC/TNM staging system. The difference in surgical outcomes between T1a and T1b ESCC therefore remains unclear. The purpose of this study was to examine the differences in surgical outcomes between T1a and T1b ESCC, and to investigate the prognostic factors in T1 ESCC. METHODS: A prospectively maintained database identified 145 previously untreated patients with pT1 ESCC who underwent radical transthoracic (n = 134) or transhiatal esophagectomy (n = 11). Median follow-up was 108 months. RESULTS: Of the 145 patients, 35 (24 %) had pT1a cancer and 110 (76 %) had pT1b cancer. Lymph node metastasis was present in 45 patients (31 %): 3 patients with pT1a cancer and 42 patients with pT1b cancer (P = 0.0003). The 5-year survival rate for the whole group was 77 %. The 5-year survival rate of the T1a patients was 94 % compared with 72 % for the T1b patients (P = 0.0282). In multivariate analysis, only the depth of tumor invasion (pT1a vs. pT1b) was an independent prognostic factor (hazard ratio 2.358; 95 % confidence interval 1.009­5.513; P = 0.0477). CONCLUSIONS: After esophagectomy, the prognosis of patients with pT1b ESCC is significantly worse than that of patients with pT1a ESCC. Infiltration into the submucosa is the only independent prognostic factor affecting survival. These findings suggested that T1a and T1b ESCC could be staged separately in the next version of UICC/TNM staging system.

Histopathological predictors for local recurrence in patients with T3 and T4 rectal cancers without preoperative chemoradiotherapy.

BACKGROUND AND OBJECTIVES: Identification of suitable predictors of local recurrence (LR) in patients with rectal cancer would be of clinical benefit. The aim of this study was to identify histopathological factors that could predict LR. METHODS: A total of 796 stage II/III patients with pT3 and pT4 rectal cancer who did not undergo preoperative chemoradiation were enrolled. LR was defined as intra-pelvic recurrence only. Histopathological factors related to LR were investigated. RESULTS: LR was found in 25 patients (6.1%) with stage II and 54 patients (13.9%) with stage IIIB/IIIC. In patients with stage II, distance of mesorectal extension (DME) >4 mm (P = 0.011) and positive venous invasion (P = 0.035) were independent factors that predicted LR. In patients with stage IIIB/IIIC, circumferential resection margin (CRM) ≤1 mm (P = 0.003) and positive lymphatic invasion (P = 0.006) were independent factors. The cumulative 5-year LR rate was higher (11.9%) in patients with a combination of DME > 4 mm and/or positive venous invasion for stage II (P < 0.001), and was also higher in patients with a combination of CRM≤1 mm and/or positive lymphatic invasion for stage IIIB and IIIC (22.2%; P < 0.002, and 34.3%; P < 0.006, respectively). CONCLUSIONS: Important histopathological predictors for LR in patients with pT3 and pT4 rectal cancer were different at each stage.

Expression of CD133 in the cytoplasm is associated with cancer progression and poor prognosis in gastric cancer.

BACKGROUND: CD133 is one of the most important stem cell markers in solid cancers. Some recent reports have described a possible relationship between CD133 and hypoxia-inducing factor-1-alpha (HIF-1α). The aim of this study was to clarify the clinical role of CD133 expression in gastric cancer and to investigate the correlation between CD133 expression and HIF-1α expression. METHODS: We studied 189 gastric cancer patients who underwent gastrectomy at Kurume University Hospital. CD133 and HIF-1α expression was examined using immunohistochemical staining. Fifty-six cases were CD133 positive, and they were divided into two expression types: luminal expression of the gland and cytoplasmic expression. We investigated the relationship among CD133 expression types, clinicopathological variables, prognosis, and HIF-1α expression. RESULTS: When comparing clinicopathological variables, expression of CD133 in the cytoplasm was related to metastasis and tumor progression. However, this relationship was not observed with luminal expression of the gland type. The survival rate in patients with cytoplasmic CD133 expression was significantly worse than that in the CD133-negative group. This relationship was observed in the survival rate of the adjuvant chemotherapy group and the curative resection group. Multivariate analysis revealed that the expression of CD133 in the cytoplasm was an independent prognostic factor in gastric cancer. Regarding the correlation between CD133 expression and HIF-1α expression, the HIF-1α positive rate was lower in patients with CD133 luminal expression of the gland type and higher in patients with cytoplasmic expression of CD133. CONCLUSION: Gastric cancer cells with CD133 expression in the cytoplasm were cells with high potential for malignancy, and this phenotype was associated with cancer progression, chemotherapy resistance, recurrence, and poor prognosis. Cytoplasmic expression of CD133 may be a useful prognostic marker in gastric cancer. Significant correlation was observed between HIF-1α expression and the immunohistochemical staining pattern of CD133.

Technical tips for intersphincteric resection: how to take out the rectum.

Intersphincteric resection (ISR) is an ideal technique that preserves the anus, regardless of whether the internal anal sphincter is removed. However, it is difficult to dissect the anterior wall of the rectum from the adjacent organs. We herein describe a safe and useful ISR technique which draws out the rectum through the anus. The intersphincteric space (ISS) between the internal and external anal sphincter muscles was first transabdominally dissected. Next, the transanal dissection was advanced into the ISS bilaterally from the posterior side without dissecting the anterior wall of the anal canal, and the sigmoid colon and rectum were drawn out through the anus. Dissection between the anterior wall of the rectum and prostate/vagina could be easily performed under direct vision. This technique enables the dissection without any risk of a positive surgical margin or unexpected bleeding, and avoids injury to adjacent organs. This technique seems to be a safe and useful dissection technique for approaching the anterior wall of the anal canal.

External sphincter resection for lower rectal and anal canal adenocarcinoma: achieving anal preservation with oncological and functional satisfaction.

Intersphincteric resection (ISR) has recently been performed for very low rectal cancer, whereas abdominoperineal resection (APR) is typically reserved for cancers extremely close to the anal verge and/or when the depth of tumor invasion is suspected to involve the intersphincteric space. This is because impairment of anal function is considered unavoidable if the external sphincter (ES) is excised. We describe our technique of ISR with ES resection and discuss its outcomes. This surgical technique may offer major clinical advantages to selected patients and should be considered as an alternative to APR, although careful consideration of anal function is required.

Usefulness of endoscopic breast-conserving surgery for breast cancer.

PURPOSE: We compared the safety, invasiveness and cosmetic outcomes between endoscopic breast-conserving surgery (endoscopic group) and surgery under direct vision (direct vision group) for treating breast cancer. METHODS: We compared 100 cases of endoscopic surgery with 150 cases of direct vision surgery. The safety was evaluated in terms of the blood loss, length of the operation and presence or absence of complications, whereas the degree of invasiveness was assessed using preoperative and postoperative leukocyte counts, neutrophil counts, interleukin (IL-6) levels and fever. The cosmetic outcome was assessed on the basis of a breast evaluation by the medical staff and the patient's subjective satisfaction. RESULTS: In both groups, serious postoperative complications were absent. No significant differences were observed in the leukocyte counts, neutrophil counts, IL-6 level or fever between the groups. An evaluation of the cosmetic outcomes by the staff showed a more favorable breast size, breast shape and scar condition in the endoscopic group. A significantly higher level of patient satisfaction was also observed in the endoscopic group. Postoperative local recurrence was absent. CONCLUSIONS: The endoscopic approach showed comparable safety and invasiveness, and provided better postoperative cosmetic outcomes than direct vision surgery. Our results suggest that endoscopic breast-conserving surgery is a potentially useful surgical method for the treatment of breast cancer.

Clinicopathological evaluation of anoxic mucosal injury in strangulation ileus.

BACKGROUND: In patients with strangulation ileus, the severity of bowel ischemia is unpredictable before surgery. To consider a grading scale of anoxic damage, we evaluated the pathological findings and investigated predictive factors for bowel gangrene. METHODS: We assessed 49 patients with strangulation ileus who underwent a laparotomy between January 2004 and November 2012. Laboratory tests and the contrast computed tomography (CT) were evaluated before surgery. According to the degree of mucosal degeneration, we classified anoxic damages into the following 3 grades. Ggrade 1 shows mild mucosal degeneration with extended subepithelial space. Grade 2 shows moderate degeneration and mucosal deciduation with residual mucosa on the muscularis mucosae. Grade 3 shows severe degeneration and mucosal digestion with disintegration of lamina propria. RESULTS: Resected bowel specimens were obtained from the 36 patients with severe ischemia, while the remaining 13 patients avoided bowel resection. The mucosal injury showed grade 1 in 11 cases, grade 2 in 10 cases, and grade 3 in 15 cases. The patients were divided into two groups. One group included grade 1 and non-resected patients (n = 24) while the other included grades 2 and 3 (n = 25). When comparing the clinical findings for these groups, elevated creatine kinase (P = 0.017), a low base excess (P = 0.021), and decreased bowel enhancement on the contrast CT (P = 0.001) were associated with severe mucosal injury. CONCLUSION: In strangulation ileus, anoxic mucosal injury progresses gradually after rapid spreading of bowel congestion. Before surgical intervention, creatine kinase, base excess, and bowel enhancement on the contrast CT could indicate the severity of anoxic damage. These biomarkers could be the predictor for bowel resection before surgery.

Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients.

Refractory bone and soft tissue sarcomas are challenging diseases to treat because of their robustness to chemotherapy. Although cancer vaccines have the potential to become an attractive treatment modality, their progress has been hampered by the presence of many subtypes of sarcomas and different human leukocyte antigen (HLA)-types. We investigated whether personalized peptide vaccination (PPV) would be feasible for the vast majority of sarcoma patients. Twenty refractory bone and soft tissue sarcoma patients with nine different subtypes and 11 different HLA-class IA phenotypes were enrolled in this study. A maximum of four HLA-matched peptides showing higher peptide-specific IgG responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the HLA-A2, -A3, -A11, -A24, -A26, -A31, and -A33 types, and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific CTL and IgG responses along with other laboratory analyses were conducted before and after vaccination. No patients were excluded by either sarcoma subtypes or different HLA-types. No severe adverse events associated with PPV were observed in any patients. Peptide-specific immunological boosting was observed in the post-vaccination samples from the majority of patients. Tumor reduction of the lung metastasis and a long stable disease was observed in each case, and the median overall survival time of the 20 cases was 9.6 months. Taken together, PPV could be feasible for the vast majority of refractory sarcoma patients because of the safety and higher rates of immunological responses regardless of the presence of different sarcoma subtypes and various HLA-types.

Expression of mesenchymal markers vimentin and fibronectin: the clinical significance in esophageal squamous cell carcinoma.

BACKGROUND: The importance of mesenchymal characteristics has not been fully elucidated in esophageal cancer. METHODS: Ten normal and 77 tumor specimens were collected. Microarray analysis was performed to analyze the expression patterns of epithelial markers, mesenchymal markers, epithelial mesenchymal transition (EMT)-related genes and stem cell markers. RT-PCR analysis was conducted to confirm the results of microarray analysis. Immunohistochemical analysis was performed to verify the level of protein expression. Statistical analysis was performed to investigate the correlation between selected genes and clinicopathological factors. RESULTS: Microarray analysis showed that epithelial markers were significantly down-regulated whereas mesenchymal markers and EMT transcription factors were up-regulated in cancer cells. Two types of gene expression patterns were found in the clustering analysis, type 1 tumors and type 2 tumors. Type 1 tumor clusters did not reveal a fixed gene expression pattern whereas type 2 tumor clusters revealed up-regulation of mesenchymal markers EMT inducers and related genes. Vimentin and fibronectin were selected to distinguish between tumor types 1 and 2. Type 2 tumors showed significantly larger tumor sizes (p < 0.0001), wider ranges of lymph node metastasis (p = 0.0057), and a more severe clinical stage (p < 0.0001) than did type 1 tumors. The prognosis of patients with type 2 tumors was significantly worse than that of patients with type 1 tumors. Univariate and multivariate analyses revealed that classification of type 2 tumors was an independent prognostic factor. CONCLUSIONS: The analysis of mesenchymal markers in esophageal cancer is useful in distinguishing patients with a poor prognosis.

Phase II trial of alternating mFOLFOX6 and FOLFIRI regimens in the first-line treatment for unresectable or metastatic colorectal cancer (KSCC0701).

OBJECTIVE: This phase II study examined the efficacy and safety of alternating regimens of mFOLFOX6 and FOLFIRI as a first-line treatment for unresectable or metastatic colorectal cancer. PATIENTS AND METHODS: Forty-eight patients were enrolled in this study. Patients received an alternating regimen of 4 cycles of mFOLFOX6 followed by 4 cycles of FOLFIRI. RESULTS: The characteristics of the study population were as follows: males/females 34/12, median age 66 years (range 43-75) and Eastern Cooperative Oncology Group performance status 0/1/2 in 37/9/0 patients. The overall response rate was 58.7% [95% confidence interval (CI) 43.9-73.5]. The median progression-free survival was 10.3 months (95% CI 7.5-11.9), and the median overall survival was 28.4 months (95% CI 22.5-35.7). Among the 47 patients evaluated for toxicity, the most common grade 3-4 adverse events were leukopenia (26%), neutropenia (55%), anemia (4%), neurotoxicity (0%), diarrhea (2%), febrile neutropenia (4%), nausea (4%), vomiting (2%), and hypersensitivity (0%). CONCLUSIONS: The results of this phase II study indicate that this alternating schedule is effective and well tolerated as a first-line treatment for unresectable or metastatic colorectal cancer. The low rate of grade 3 neurotoxicity is also promising.

Extramural extension as indicator for postoperative adjuvant chemotherapy in Stage IIA (pT3N0) colon cancer.

The usefulness of adjuvant chemotherapy (CMT) in patients with Stage IIA colon cancer remains unclear. The present study aimed to investigate extramural extension as an indicator for adjuvant CMT. Data were reviewed from 202 consecutive patients with Stage IIA colon cancer that underwent curative surgery between 1995 and 2007. The distance of the extramural extension (DEE) was measured histologically. The optimal prognostic cut-off point of the DEE for oncologic outcomes was statistically determined. The eligible surviving patients had been followed for a median period of 75 months (range: 2-210 months). Patients were subdivided into two groups according to the optimal cut-off point; DEE ≤5 mm (pT3a) and DEE >5 mm (pT3b). The pT3b was the most powerful independent risk factor for postoperative recurrence (P = 0.0324, HR: 3.04, 95% CI: 1.098-8.408), and was significantly correlated with distant metastasis (P = 0.0161 HR: 5.19, 95% CI: 1.765-15.239). The recurrence-free and cancer-specific 5-year survival rates in patients with pT3b were significantly lower than in patients with pT3a (81.5% vs. 95.4%, P = 0.0003 and 85.9% vs. 97.4%, P = 0.0007, respectively). pT3b could be an important risk factor for distant metastasis in Stage IIA colon cancer. Postoperative adjuvant CMT may be indicated for patients with pT3b.

Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer.

BACKGROUND: Hypoxia is a common feature of rapidly growing solid tumors. Therefore, cellular adaptation to hypoxia and altered glucose metabolism are fundamental to the biology of cancer cells. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor for more than 60 genes recognized to control the delivery of oxygen and nutrients through the induction of angiogenesis and glycolysis under hypoxic conditions. Therefore, inhibition of the expression of HIF-1α can be expected to be potentially tumor-specific molecular target-based therapy. In this study, we evaluated the significance of HIF-1α expression in relationship to clinicopathological factors, prognosis, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD). METHODS: Paraffin-embedded tumor specimens from 128 patients who underwent gastrectomy at Kurume University from 2004 to 2005 were used to assess the clinical significance of HIF-1α expression. We used the ABC method to perform an immunohistochemical analysis of the HIF-1α and VEGF expression. RESULTS: Eighty-four (65.6%) of gastric cancer specimens were positive for HIF-1α expression. Multivariate analysis showed that histology, depth of invasion, VEGF expression, and MVD were significantly associated with HIF-1α expression. On relapse-free and overall survival curves, the HIF-1α-negative group was significantly higher than the HIF-1α-positive group. Moreover, HIF-1α(+)/VEGF(+) patients had the worst prognosis. HIF-1α expression was identified as a significant predictor of relapse-free survival and overall survival by multivariate Cox's proportional hazard analyses. CONCLUSION: Overexpression of HIF-1α was found to be an indicator of poor prognosis for patients with gastric cancer and was significantly correlated with histology, depth of invasion, VEGF, and MVD.

Initial report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japanese patients.

BACKGROUND: A prospective feasibility study was planned to clarify the proportion of compliance and adverse events in the administration of capecitabine as adjuvant chemotherapy for colon cancer in Japanese patients. METHODS: We aimed initially to register 92 cases of R0 stage III colon cancer. Capecitabine (2,500 mg/m(2)/day) was given orally on days 1-14 every 3 weeks for 8 cycles. The proportion of treatments completed as planned was selected as the primary endpoint. RESULTS: Ninety-seven cases were registered and treated between September 2008 and August 2009. The proportion of treatments completed in the full analysis set was 64/97 [66.0%; 95% confidence interval (CI), 55.7-75.3%] and in the per protocol set was 64/91 (70.3%; 95% CI, 59.8-79.5%). Adverse events which led to treatment discontinuation included hand-foot syndrome (HFS) (7), haematotoxicity (5) and increased hepatic damage (4). The proportions of patients with major grade 3/4 adverse events were HFS 22.7%, neutropenia 7.2%, diarrhoea 2.1%, and increased bilirubin 0.0%. CONCLUSIONS: This collaborative multi-facility study, the first of its kind in Japan, presented results of a safety confirmation experiment on capecitabine as adjuvant chemotherapy for stage III colon cancer. The results suggest that capecitabine may be administered safely to Japanese patients.

Expression of p27Kip1 protein in gastric carcinoma.

BACKGROUND/AIMS: p27 protein resulted in the accumulation of cyclin E/cyclin dependent kinase 2/p27 ternary complexes inhibits gap1 to synthesis phase transition. Here, we have investigated the correlations, if any, between the expressions of p27 and p53, and proliferation cell nuclear antigen. METHODOLOGY: A retrospective study was performed on 75 cases of gastric cancer that had undergone surgical resection. Immunohistochemical staining was performed using the avidin-biotin-peroxidase complex technique method, with anti-p27 antibody, anti-p53 antibody and anti-proliferation cell nuclear antigen antibody. RESULTS: The rate of lymph node metastasis in the p27 negative cases was significantly higher than that in the p27 positive cases.The rate of tumor limited to the gastric wall in the p27 positive cases was significantly higher than-that in the p27 negative cases.The mean proliferation cell nuclear antigen index of the p27 negative cases was significantly higher than that of the p27 positive cases. The survival rate of the p27 positive cases was significantly higher than that of the p27 negative cases. In Stage III cases, the survival rate of the p53 negative p27 positive or p53 negative p27 negative cases was significantly higher than that of p53 positive p27 negative cases. CONCLUSIONS: p27 was correlated with lymph node metastasis, depth of invasion, and proliferative activity of gastric cancer. Immunoreactivity of combination of p53 and p27 was a useful predictive marker of prognosis of gastric cancer.

Intersphincteric resection for very low rectal cancer: a systematic review.

Radical surgical treatment for very low rectal cancer near the anus has generally involved abdominoperineal resection. Various sphincter-saving operations have been developed for such tumors to optimize the patients' postoperative quality of life. Current protocols focus on intersphincteric resection (ISR), which differs from conventional hand-sewn coloanal anastomosis (CAA) after low anterior resection. However, the efficacy of ISR remains unclear. The surgical, oncologic, and functional outcomes after intersphincteric resection (ISR) were reviewed. This review of the current literature was conducted by searching the PubMed online database. Articles focusing specifically on conventional hand-sewn CAA were excluded from this study. The mean mortality rate is <2 %, and the mean morbidity rate ranges from 7.7 to 38.3 %. The mean local recurrence rate varies widely from 0 to 22.7 %, with a mean follow-up duration of 40-94 months. The mean disease-free and overall 5-year survival rates are 69-86 and 79-97 months, respectively. Functional outcomes are generally acceptable, but accurate evaluation is extremely difficult due to the absence of unified appraisal methods. ISR appears surgically, oncologically and functionally acceptable. However, more experience and better understanding of the oncology, anal physiology, and pelvic anatomy are necessary to achieve successful outcomes without complications, and to improve patient survival.

Randomized controlled trial comparing antioxidant-enriched enteral nutrition with immune-enhancing enteral nutrition after esophagectomy for cancer: a pilot study.

PURPOSE: The objective of this study was to compare the effects of two types of enteral supplements, an antioxidant-enriched enteral nutrition (AeEN) and an immune-enhancing enteral nutrition (IeEN), on the nutrition, immunoinflammatory response, antioxidant capacity and clinical outcomes in patients after esophagectomy for cancer. METHODS: Patients (n = 20) undergoing esophagectomy for cancer were randomized in this single-center, open-label study. Two types of enteral supplements were used for 5 days before surgery and 7 days after surgery. The circulating levels of nutritional markers, immunoinflammatory markers, oxidative stress markers, and the antioxidant capacity were compared throughout the perioperative period, and the patients' clinical outcomes were also compared. RESULTS: The circulating levels of nutritional markers decreased after surgery, but the changes were not significantly different between the AeEN group and the IeEN group throughout the perioperative period. Surgery increased the immunoinflammatory markers, and the levels were not significantly different between the groups after surgery. Surgery also increased the levels of oxidative stress markers, but there were no significant differences between the groups throughout the study period. CONCLUSIONS: The results of this pilot study suggest that AeEN and IeEN have a similar effect on nutrition, the immunoinflammatory response, antioxidant capacity and clinical outcomes after esophagectomy for cancer. These findings, therefore, warrant further studies on a larger scale.

[A long-term survivor of advanced gallbladder carcinoma treated with curative operation and hepatic arterial infusion].

60-year-old woman was referred to us for epigastralagia under the diagnosis of chronic cholecystitis. Cholecystectomy was performed, and gallbladder carcinoma was pinpointed by postoperative pathological diagnosis. Because liver invasion should have been detected by pathological diagnosis, we conducted liver S4a+S5 resection, extrahepatic bile duct resection and D2 lymphadenectomy. The pathological diagnosis was advanced gallbladder carcinoma with liver metastasis. We treated a patient with curative operation and hepatic arterial infusion adjuvant chemotherapy by low-dose FP therapy for advanced gallbladder carcinoma, and she is doing well now without disease recurrence eight years after surgery.