Laparoscopic polyglycolic acid spacer placement for locally recurrent rectal cancer.

Carbon ion radiotherapy (CIRT) has received attention for the treatment of locally recurrent rectal cancer. When the surrounding primary organs are close to the irradiation site, a spacer is required to ensure safe irradiation. This work describes a novel technique using a bioabsorbable polyglycolic acid spacer placed laparoscopically and presents a technical report with five case studies. The short-term surgical outcomes were as follows: mean operating time 235 min with blood loss of 38 mL. CIRT was planned, and the patients underwent irradiation within 2 months of surgery. No pelvic infections occurred, and all procedures were performed safely. Herein, were present a technical report with reference to a video of the surgical procedure.

Retrospective study of an incisional hernia after laparoscopic colectomy for colorectal cancer.

PURPOSE: This study aimed to examine the incidence of incisional hernia (IH) in elective laparoscopic colorectal surgery (LC) using regulated computed tomography (CT) images at intervals every 6 months. METHODS: We retrospectively examined the diagnosis of IH in patients who underwent LC for colorectal cancer at Kansai Medical University Hospital from January 2014 to August 2018. The diagnosis of IH was defined as loss of continuity of the fascia in the axial CT images. RESULTS: 470 patients were included in the analysis. IH was diagnosed in 47 cases at 1 year after LC. The IH size was 7.8 cm2 [1.3-55.6]. In total, 38 patients with IH underwent CT examination 6 months after LC, and 37 were already diagnosed with IH. The IH size was 4.1 cm2 [0-58.9]. The IH size increased in 17 cases between 6 months and 1 year postoperatively, and in 1 case, a new IH occurred. 47%(18/38) of them continued to grow until 1 year after LC. A multivariate analysis was performed on the risk of IH occurrence. SSI was most significantly associated with IH occurrence (OR:5.28 [2.14-13.05], p = 0.0003). CONCLUSION: IH occurred in 10% and 7.9% at 1 year and 6 months after LC. By examining CT images taken for the postoperative surveillance of colorectal cancer, we were able to investigate the occurrence of IH in detail.

p62 is a useful predictive marker for tumour regression after chemoradiation therapy in patients with advanced rectal cancer: an immunohistochemical study.

AIM: This study aimed to evaluate the relationship between p62 expression status and tumour regression grade in advanced rectal cancer. METHODS: We enrolled 47 consecutive patients with advanced rectal cancer who underwent chemoradiation therapy (CRT) before surgery. p62 expression in the biopsy specimens was immunohistochemically evaluated, and p62 expression score (staining intensity × positive tumour cells, %) was calculated (range 0-300). The relationship between p62 expression score and CRT effect was analysed. RESULTS: The staining intensity was +2 and +3 in 29 and 18 patients, respectively. The median proportion of positive neoplastic cells was 87.8%, and that of the p62 expression score was 200. Stronger staining intensity and a higher proportion of p62-positive neoplastic cells were significantly associated with CRT non-effectiveness (P = 0.0002 and P = 0.0116, respectively), and a higher p62 expression score was significantly associated with CRT non-effectiveness (P < 0.0001). The optimal cut-off value for predicting the CRT effect was 240. CONCLUSIONS: A higher p62 expression score was significantly associated with less CRT effectiveness in patients with advanced rectal cancer. Analysis of p62 expression score using biopsy specimens is a useful and easily assessable prediction marker for CRT effect and might help select patients who can undergo a 'watch-and-wait' strategy after CRT.

[Diagnosis of Serous Adenocarcinoma following Pneumatosis Intestinalis Development during Bevacizumab Therapy for Cancer of Unknown Primary-A Case Report].

A 75-year-old woman was treated with TC plus Bev for cancer of unknown primary. During treatment, she presented to the clinic with chief complaints of general malaise and anorexia. On presentation, abdominal distention and upper abdominal tenderness were noted, and sepsis was suspected. A thoracoabdominal CT scan revealed prominent intramural emphysema and mesenteric gas in the ascending colon. An emergency laparotomy was performed for suspected pneumatosis intestinalis non-obstructive intestinal ischemia. However, no intra-abdominal contamination or ischemic changes were observed intraoperatively. Histological examination revealed a small adenocarcinoma on the serous surface of the ascending colon, and immunochemical staining confirmed the diagnosis of serous adenocarcinoma as the patient's primary cancer. This report describes a case in which the patient achieved long-term survival after diagnosis. It also emphasizes the importance of identifying the subset of patients with cancer of unknown primary who have a good prognosis in order to provide appropriate treatment.

Feasibility of needlescopic surgery for colorectal cancer: safety and learning curve for Japanese Endoscopic Surgical Skill Qualification System-unqualified young surgeons.

BACKGROUND: Needlescopic surgery (NS) is a minimally invasive technique for colorectal cancer. NS may be easier to perform than other minimally invasive surgery such as single-incision laparoscopic surgery and natural orifice transluminal endoscopic surgery because the port setting is the same while the shafts are thinner than in conventional laparoscopic surgery. We evaluated the capability of introducing this surgery for sigmoid and rectosigmoid colon cancer by assessing the learning curve in Japanese Endoscopic Surgical Skill Qualification System (JESSQS)-unqualified surgeons. METHODS: In this retrospective study, 112 cases of sigmoidectomy and anterior resection were performed by NS from October 2011 to December 2015 in our institution. Surgical outcomes including operation time, blood loss, postoperative hospital stay, perioperative complications, and overall survival were compared between JESSQS-qualified surgeons (Group A) and JESSQS-unqualified surgeons (Group B). The learning curve for NS was established using the average operation times in JESSQS-unqualified surgeons. RESULTS: Groups A and B comprised of 41 and 71 patients, respectively. Ninety patients underwent sigmoidectomy and 22 patients underwent anterior resection. No conversion to open surgery occurred. The operation time was significantly shorter in Group A than B (P = 0.0080). There were no significant differences in blood loss, the postoperative hospital stay, perioperative complications, or overall survival between the two groups. These variables were similar even when NS was considered relatively difficult, as in patients with obesity (body mass index of ≥ 25 kg/m2), bulky tumors (tumor size of ≥ 50 mm), and stage III/IV cancer. The average operation time in JESSQS-unqualified young surgeons was significantly shorter in the ninth and tenth cases than in the first and second cases of NS (P = 0.0282). CONCLUSIONS: NS for sigmoid and rectosigmoid colon cancer was performed safely by both JESSQS-qualified surgeons and JESSQS-unqualified surgeons. Even JESSQS-unqualified young surgeons might be able to quickly learn NS techniques.

Pretreatment Serum Carbohydrate Antigen 19-9 Concentration Is a Predictor of Survival of Patients Who Have Undergone Curative Resection of Stage IV Rectal Cancer.

BACKGROUND: To evaluate whether pretreatment carcinoembryonic antigen and carbohydrate antigen (CA)19-9 are useful predictors of survival in patients with stage IV rectal cancer who have undergone curative resection. METHODS: In this retrospective study, data on 73 patients who had undergone curative resection of stage IV rectal cancer were reviewed. Associations between various clinicopathological factors and survival outcomes were analyzed. RESULTS: According to univariate analysis, elevated pretreatment CA19-9 (p = 0.0028), R1 resection (p = 0.0318), and mucinous or poorly differentiated adenocarcinoma (p = 0.0228) were significantly associated with poor overall survival (OS), and lymph node metastasis (p = 0.0211) was significantly associated with poor disease-free survival (DFS). Multivariate analyses showed that elevated pretreatment serum CA19-9 concentration (hazard ratios [HR] 3.33; 95% CI 1.24-9.42; p = 0.0174) was an independent predictor for OS and lymph node metastasis (HR 2.26; 95% CI 1.15-4.82; p = 0.0164) was an independent predictor for DFS. Among 55 patients with recurrences after curative resection, the rate of complete resection of recurrences was significantly higher in patients with normal pretreatment CA19-9 than in those with elevated CA19-9 (p = 0.049). Post-recurrence survival was significantly worse in patients with elevated pretreatment CA19-9 than in those with normal CA19-9 (p = 0.0196). CONCLUSIONS: Pretreatment CA19-9 is good predictor of survival after curative resection of stage IV rectal cancer.

Appendiceal Metastasis of Breast Cancer: A Case Report and a Literature Review.

Appendiceal metastases of breast cancer (BC) are very rare, and there are few reports of resection. Asymptomatic appendiceal enlargement is often suspected to be a primary appendiceal tumor, making it difficult to suspect metastatic tumors, especially metastases from BC. On the other hand, advances in drug therapy, including hormonal therapy for BC, have prolonged survival, and there is a possibility of encountering metastatic cases that have rarely been seen before. We herein present a case in which an enlarged appendix, identified during hormonal therapy for advanced BC, was laparoscopically removed and diagnosed as BC metastasis. A 53-year-old woman had been diagnosed with invasive ductal carcinoma (IDC) based on a breast biopsy, and the appendiceal specimen was diagnosed as invasive lobular carcinoma (ILC). We herein report this unique case and provide a detailed review of 13 previous reports.

Practical use of transanal decompression tube following the repair of fourth-degree perineal tears associated with vaginal delivery.

BACKGROUND: Fourth-degree perineal tears associated with vaginal delivery (PTAVD) occur in approximately 0.25 to 6% of vaginal deliveries. A persistent challenge in treating fourth-degree PTAVD is the high incidence of anastomotic leakage, leading to impaired quality of life, marked by incontinence, rectovaginal fistula, and painful sexual intercourse. Thus, effective interventions are necessary. Herein, we report our successful approach in repairing a fourth-degree PTAVD, involving the placement of a transanal decompression tube (TDT) during the early postoperative period. CASE PRESENTATION: Five patients underwent the repair of fourth-degree PTAVD by suturing the mucosal and muscular layers of the rectum, and the vaginal wall in layers. Subsequently, a TDT was placed in the rectum, positioned 10-15 cm from the anal verge. The TDT was allowed to drain spontaneously without suction. Gastrografin enema examination was performed through a TDT, followed by a computed tomographic scan on postoperative days 3-4. After unfavorable complications were ruled out, the TDT was removed and the patients were transitioned to a normal diet. RESULT: All patients showed favorable outcomes with no occurrence of vaginal fistula or incontinence. CONCLUSION: This simple intervention demonstrates potential efficacy in reducing anastomotic leakage following the repair of fourth-degree PTAVD.

Analysis of the clinicopathological features of tailgut cyst with emphasis on the development of neoplastic lesions.

Tailgut cyst is a rare congenital cyst occurring in the retrorectal space and development of neoplastic lesions in tailgut cyst has been reported. Due to the rarity of the tumor, the histogenesis of neoplastic lesions in tailgut cyst has remained elusive. In the present study, the clinicopathological features of tailgut cyst were analyzed with a particular focus on the development of neoplastic lesions. The clinicopathological features of four patients with tailgut cyst (one female and three males) were retrospectively reviewed. No symptoms were present in two patients. Perineal discomfort, and constipation and urinary retention, were described in the other two patients, respectively. Magnetic resonance imaging showed that the cystic lesions were hypointense on T1- and hyperintense on T2-weigted images in all patients. Histopathological analysis revealed that all lesions were multilocular, and cystic walls were covered by squamous and ciliated epithelia without nuclear atypia. The development of neoplastic lesions was noted in two patients. Dysplastic change composed of piling-up proliferation of glandular cells with mild to moderate nuclear atypia was present in one patient, and invasive adenocarcinoma with a dysplasia component was observed in another patient. Dysplasia of the glandular cells, as seen in two patients in the present series, may be a precursor lesion of invasive adenocarcinoma; therefore, adenocarcinoma arsing in tailgut cyst may show a dysplasia-carcinoma sequence. While the reported incidence of neoplastic lesions in tailgut cysts is ~9% or less, their frequency remains to be accurately determined. Therefore, complete surgical resection is important for the management of patients with tailgut cyst. Additional clinicopathological and molecular studies with large cohorts may be required to clarify the histogenesis of neoplastic lesion in tailgut cyst.

Prognostic scoring system based on indicators reflecting the tumor glandular differentiation and microenvironment for patients with colorectal cancer.

Prognostic stratification is an urgent concern for patients with colorectal cancer (CRC). The desmoplastic reaction (DR) is speculated to mirror the tumor microenvironment. DR types are considered independent prognostic indicators in CRC, but have not been incorporated in previous prognostic nomograms. We aimed to assess the prognostic significance of a novel approach incorporating histopathological indicators reflecting tumor glandular differentiation and microenvironment. We evaluated 329 consecutive patients with CRC who underwent surgical resection at Kansai Medical University. Histological glandular differentiation was scored as 2 (0 point), 3 (1 point), or 4 (2 points). Tumor buddings (TBs) were classified as TB1 (0 point), TB2 (1 point), or TB3 (2 points). pT1 or 2 was considered as 0 point, pT3 or 4 + DR non-immature type as 1 point, and pT3 or 4 + DR immature type as 2 points. Lymph node metastasis was classified as pN0 (0 point), pN1 (1 point), or pN2 (2 points). The preoperative carcinoembryonic antigen levels were categorized as < 5.0 ng/mL (0 point) and ≧5.0 (1 point). Considering these factors, the following D&M (tumor differentiation and microenvironment) scoring system was applied: I (0-2 points), II (3-4 points), III (5-6 points), and IV (7-9 points). Kaplan-Meier curves showed significant differences in disease-specific survival and recurrence-free survival among the assigned scores, highlighting their enhanced utility compared with the American Joint Committee on Cancer 8th edition staging system. The D&M scoring system was valuable as the initial prognostic nomogram, including DR.

Two cases of malignant peritoneal mesothelioma without asbestos exposure: cytologic and immunohistochemical features.

Approximately half a century has passed since asbestos was first reported to be the main cause of malignant mesothelioma; yet the incidence of this disease continues to increase worldwide. Twenty percent of cases occur without prior asbestos exposure, and in these patients, malignant peritoneal mesothelioma is more common than malignant pleural mesothelioma. Here, we report the cytomorphologic and immunohistochemical features of 2 cases of malignant peritoneal mesothelioma where there was no history of asbestos exposure. Ascitic cytology showed that most cells were isolated and that clusters were rarely observed, but the findings were consistent with malignant mesothelioma in both cases. Immunohistochemical analysis for epithelial membrane antigen, calretinin, vimentin, ß-catenin, melan-A, glucose transporter-1, cytokeratin CAM5.2, Wilms tumor antigen-1, D2-40, CD146, progesterone receptor, estrogen receptor, and cytokeratin 5/6 was indicative of malignant mesothelioma. In malignant mesothelioma without prior asbestos exposure, the etiology and prognostic significance is still unclear. Further study is needed to clarify this point.

[Asymptomatic longterm survival in a patient with sigmoid colon lymph node metastasis with cancerous ascites of unknown origin].

A 63-year-old man bearing a palpable tumor had a lymph node metastasis adjacent to the sigmoid colon that was detected by computed tomography and positron emission tomography. The sigmoid colon and enlarged lymph nodes were surgically resected, and cancerous ascites were present. Pathologically, the tumor in the lymph node was a poorly-differentiated adenocarcinoma that was positive for CA19-9 as well as CK7(-/+), CK20(+/-), VEGF(+), p 53(+)and MIB-1 (>10%). We treated this case as a pancreatic or bile duct carcinoma due to the patient's markedly elevated serum levels of CA19-9 and SPan-1. However, we could not make a conclusive diagnosis. Gemcitabine-based chemotherapy was administered, and the patient had no signs of recurrence for 24 months after the operation. Then, a recurrence was identified by imaging studies, and the chemotherapy was changed to paclitaxel and carboplatin. The patient had stable disease until tumor regrowth was identified 38 months after the operation, chemotherapy was then stopped. However, at 48 months after the operation, the patient remains well and has no symptoms. Our case suggests that surgery and the appropriate choice of anticancer drugs may contribute to the long-term survival of patients with cancer of an unknown primary origin.

Case report: administration of immune checkpoint inhibitor for SMARCB1 (INI1)-negative rhabdoid carcinoma with microsatellite instability (MSI)-high in the right colon.

BACKGROUND: Malignant tumors with rhabdoid features are rare, highly aggressive, and some of them are characterized by SMARCB1 (INI1) loss. Although cases of rhabdoid carcinoma are extremely rare, its occurrence in the colon has been reported previously. CASE PRESENTATION: A 71-year-old Japanese female patient presented with loss of appetite, fatigue, and weight loss. Computed tomography demonstrated a tumor in the right colon that infiltrated the surrounding kidneys and swelling of the left supraclavicular and periaortic lymph nodes. Laparotomy revealed that the tumor was unresectable because it had directly invaded the head of the pancreas and duodenum. Therefore, ileocecal vascularized bulky lymph nodes were sampled, and gastrojejunostomy with Braun's anastomosis and ileotransversostomy were performed as palliative procedures. Histopathological examination of the lymph nodes revealed that the neoplastic cells had rich eosinophilic cytoplasm and eccentrically located large nuclei characteristic of rhabdoid carcinoma. In addition, these neoplastic cells lacked SMARCB1 expression; therefore, the patient was diagnosed with SMARCB1-negative rhabdoid carcinoma. The postoperative course was uneventful. Molecular analysis confirmed that the neoplastic cells had high microsatellite instability (MSI); therefore, two cycles of pembrolizumab were administered. However, no clinical benefit was noted, and the patient died 3 months postoperatively. CONCLUSION: This is the first report of a case of SMARCB1-negative rhabdoid colon carcinoma with high MSI treated with pembrolizumab. Rhabdoid carcinoma is highly aggressive; therefore, additional studies are required to determine the therapeutic strategy for SMARCB1-negative rhabdoid colorectal carcinoma.

Significance of desmoplastic reactions on tumor deposits in patients with colorectal cancer.

It has been well recognized that the tumor microenvironment serves important roles in the progression and invasion of cancer. The desmoplastic reaction (DR) is a fibrous tissue reaction around tumor cells, and the prognostic significance of DR in colorectal cancer (CRC) has been established. Tumor deposits (TD) are also an important prognostic indicator of CRC. Notably, immature type DR has been linked to poor prognosis. In addition, immature type DR is significantly associated with a higher pT stage, presence of lymphovascular invasion and lymph node metastasis; however, to the best of our knowledge, the association between DR and TD has not yet been examined. The present study aimed to clarify this association. This study included 443 consecutive patients with pT3 or pT4 CRC who underwent surgical resection. The histopathological features, including DR and TD, were evaluated. Statistical analyses of the presence of TD, DR and other clinicopathological parameters were performed. The present cohort included 205 female and 238 male patients; 293 (66.1%) and 150 (33.9%) patients were classified as pT3 and pT4, respectively. Immature, intermediate and mature DR were noted in 282 (63.7%), 91 (20.5%) and 70 patients (15.8%), respectively. TD was observed in 93 (21.0%) patients. Immature type DR was significantly associated with a higher pT stage (P<0.0001), presence of lymph node metastasis (P<0.0001), lymphatic (P=0.0007), venous (P<0.0001) and perineural invasion (P<0.0001), and higher tumor budding (TB) (P<0.0001). Moreover, immature type DR was significantly associated with the presence of TD (P<0.0001). The present study demonstrated a significant association between immature type DR and the presence of TD, and suggested a close relationship between lymphovascular invasion, DR, TB and TD. Additional studies are required to analyze the detailed mechanism underlying the development of immature DR in CRC to define novel treatment strategies.

Retinal degeneration induced in adult mice by a single intraperitoneal injection of N-ethyl-N-nitrosourea.

Seven-week-old female BALB/c mice received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (50, 100, 200, 400, or 600 mg/kg), and retinal damage was evaluated after 7 days. Sequential morphological features of the retina and retinal apoptosis, as determined by the TUNEL assay, were analyzed 6, 12, 24, and 72 hr and 7 days after treatment with 600 mg/kg of ENU. Moreover, older mice (25 to 34 weeks of age) received an intraperitoneal injection of 600 mg/kg ENU and were sacrificed 7 days later. All animals were necropsied, and both eyes were examined histopathologically. Two of the 5 mice that received 600 mg/kg ENU died during the experimental period. Histopathologically, all mice that received 600 mg/kg of ENU experienced retinal degeneration characterized by the loss of photoreceptor cells (disappearance of the outer nuclear layer and photoreceptor layer) in both the central and peripheral retina within 7 days. One of 5 mice treated with 400 mg/kg ENU exhibited retinal damage that was restricted to the central retina. Older mice treated with 600 mg/kg ENU exhibited retinal damage that was similar to the retinal damage in younger mice. In the 600 mg/kg ENU-treated mice, TUNEL-positive photoreceptor cells peaked 72 hr after ENU treatment. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after treatment. In conclusion, ENU induces retinal degeneration in adult mice that is characterized by photoreceptor cell apoptosis.

Pathological Complete Response of Clinical T4b Ascending Colon Cancer after Preoperative Chemotherapy Using Pembrolizumab.

Preoperative chemotherapy is efficacious in several cancers. However, it is not an established treatment for locally advanced colon cancer, particularly cases with microsatellite instability-high (MSI-H)/deficient mismatch repair. Herein, we report a case of pathological complete response of MSI-H clinical T4b ascending colon cancer to preoperative treatment with pembrolizumab. A 78-year-old man was diagnosed with ascending colon cancer that invaded into the iliacus muscle and enlarged regional lymph nodes. The tumor was classified as T4bN1bM0 stage IIIC according to the 8th Union for International Cancer Control guidelines, with MSI-H status. Based on our initial diagnosis, this tumor could not be resected completely. Thus, the patient underwent preoperative therapy with CAPOX (capecitabine and oxaliplatin combination) plus bevacizumab. After 4 cycles of preoperative CAPOX/bevacizumab, we observed tumor reduction corresponding to a partial response based on the Response Evaluation Criteria in Solid Tumors criteria. Nevertheless, tumor invasion of the iliacus muscle persisted. Since oxaliplatin-induced peripheral sensory neuropathy was observed, we discontinued treatment with oxaliplatin and changed the regimen to pembrolizumab in anticipation of the therapeutic effect of this immune checkpoint inhibitor against MSI-H tumors. After 2 cycles of therapy with pembrolizumab (200 mg/body on day 1 every 3 weeks), there was drastic tumor regression. In addition, computed tomography indicated that all lymph node metastases had disappeared. Therefore, the patient underwent laparoscopic right hemicolectomy with D3 lymph node dissection. Analysis of the resected specimen showed pathological complete response.

Two cases of primary solitary fibrous tumor in the pelvis resected using laparoscopic surgery.

BACKGROUND: We report two resected cases of solitary fibrous tumors (SFT) that were accidentally found in the pelvic cavity. CASE PRESENTATION: Case 1 was a 54-year-old male. A colonoscopy for the examination of intestinal polyps revealed an extramural tumor in the right anterior wall of the low rectum. A preoperative MRI showed a well-demarcated T1 low and T2 mixed intensity extramural tumor (53 × 36 mm) located right lateral to the low rectum and behind the seminal vesicle. Laparoscopic surgery was successful for tumor extirpation. Immunohistochemical examination of the specimen revealed STAT6 (+) and CD34 (+) cells, a Ki67 positivity of 7-8%, a mitotic index of 4-5/50 HPF, and a diagnosis of SFT. There was no recurrence 29 months after surgery. Using RT-PCR and sequencing, we detected the NAB2-STAT6 fusion gene but the locus of genomic inversion was not detected. Case 2 was a 43-year-old male that received conservative treatment for appendicitis. A CT scan accidentally revealed a tumor of 40 mm of length in the left obturator area. A MRI revealed a well-demarcated T1 and T2 high intensity tumor. The patient underwent surgical biopsy. Immunohistochemical examination of the biopsy revealed STAT6 (+) and CD34 (+) cells, Ki67 positive cells < 1%, and a diagnosis of SFT. We could not detect the NAB2-STAT6 fusion gene in the extirpated tumor. CONCLUSIONS: Two cases of pelvic SFT were diagnosed by immunohistochemical examination, RT-PCR and sequencing and successfully resected by laparoscopic surgery.

Skeletal muscle loss is an independent negative prognostic factor in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy.

BACKGROUND: The impact of body composition on the short- or long-term outcomes of patients with surgically treated advanced rectal cancer after neoadjuvant chemoradiotherapy remains unclear. This study examined the correlation between low skeletal muscle mass and morbidity and survival in patients with advanced lower rectal cancer. METHODS: We enrolled 144 clinical stage II/III patients with advanced lower rectal cancer who underwent neoadjuvant chemoradiotherapy followed by curative resection between 2004 and 2011. The cross-sectional skeletal muscle area at the third lumbar vertebra (L3) level was evaluated by computed tomography before chemoradiotherapy, and this was normalized by the square of the height to obtain the skeletal muscle index. Low skeletal muscle mass was defined as the sex-specific lowest quartile of the L3 skeletal muscle index. The association between low skeletal muscle mass and morbidity, relapse-free survival, or overall survival was assessed. RESULTS: Low skeletal muscle mass was identified in 37 (25.7%) patients. Age and body mass index were associated with low skeletal muscle mass. By multivariate analysis, we found that low skeletal muscle mass was independently associated with poor overall survival (hazard ratio = 2.93; 95%CI: 1.11-7.71; p = 0.031) and relapse-free survival (hazard ratio = 2.15; 95%CI: 1.06-4.21; p = 0.035), but was not associated with the rate of postoperative complications. CONCLUSIONS: Low skeletal muscle mass is an independent negative prognostic factor for relapse-free and overall survival in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy.

Requirement of p38 MAPK for a cell-death pathway triggered by vorinostat in MDA-MB-231 human breast cancer cells.

Vorinostat is a histone deacetylase inhibitor that effectively suppresses cancer-cell proliferation by inducing cell-cycle arrest and/or apoptosis. We now show the involvement of p38 mitogen-activated protein kinase (MAPK) in the regulation of vorinostat-induced apoptosis in MDA-MB-231 human breast cancer cells. Vorinostat induced the hyperacetylation of histone H3, which correlated to apoptosis induction. Vorinostat-induced apoptosis occurred in parallel with the phosphorylation of p38 MAPK and the dephosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). Knockdown of p38 MAPK prominently abrogated apoptosis induction and was accompanied by decreased caspase-3 cleavage. These findings support the notion that the activation of the p38 MAPK pathway followed by caspase-3 cleavage is responsible for vorinostat-induced apoptosis in MDA-MB-231 cells.