[Two Cases of Metastatic Colorectal Cancer Treated with TAS-102 plus Bevacizumab].

Trifluridine/tipiracil (TAS-102) is an important chemotherapeutic agent recommended by the Japanese guidelines as third- or fourth-line treatment for colorectal cancer. Some studies have reported that administration of TAS-102 concomitant with bevacizumab prolongs progression-free and overall survival in colorectal cancer. We describe 2 patients treated with a chemotherapeutic regimen comprising TAS-102 concomitant with bevacizumab for recurrent colorectal cancer. No adverse events ≥Grade 3(except for hematotoxicity)were observed in these patients. The patient received several courses of chemotherapy with adjustments of the dose and dosing intervals to prevent neutropenia. Combination therapy using TAS-102 and bevacizumab is a feasible Late-line chemotherapeutic regimen for colorectal cancer.

[Case of Peritoneal Dissemination from Gastrointestinal Stromal Tumor of Jejunum Treated with Repeated Non-Curative Surgery].

A 71-year-old male presented with abdominal distension and fever to our hospital. Abdominal CT revealed a huge tumor in abdomen, and non-curative surgery was performed. Peritoneal dissemination was widespread and the tumor invaded the bladder and sigmoid-colon mesenterium. Two months after the initial surgery, CT showed liver metastasis, and oral administration of imatinib mesylate was started. The peritoneal dissemination and liver metastasis showed a decrease, and this was well controlled for 45 months without severe side effects. Abdominal CT revealed peritoneal dissemination in the ileocecum after 43 months since the administration of imatinib. Therefore, sunitinib treatment was initiated. After 3 months of sunitinib administration, the tumor perforated. Emergency operation was performed to resect the ileocecum, and sunitinib was continued for 1 year. In GIST with liver metastasis and peritoneal dissemination, repeated surgical resection combined with chemotherapy is important to improve the patient's survival.

[Long-Term Survival of Gastric Cancer with Multiple Liver and Lymph Node Metastases-A Case Report].

Currently, chemotherapy against unresectable advanced gastric cancer is progressing with the development new drugs and due to results of several clinical trials. Here, we reported a case of long-term survival of gastric cancer with multiple liver and lymph node metastases. A 68-year-old man was diagnosed with gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple liver metastases at another hospital. He was referred to our hospital from Yamashita Naika Syokakika. We administrated 4 courses of S-1 plus CDDP. The main tumor and all metastatic lesions were significantly reduced. Subsequently, total gastrectomy, partial liver resection, and left neck and para-aortic lymph node resection(conversion surgery)were performed. The cancer cell was remnant at the main tumor and para-gastric lymph node. No cancer cells were detected in another lesion(R0 resection). Postoperatively, only S-1 was administered. However, 28 months after undergoing gastrectomy, liver metastasis occurred. Therefore, S-1 plus oxaliplatin, paclitaxel plus ramucirumab, and CPT-11 plus CDDP were administered. Liver metastases again increased and decreased, respectively. However, 46 months after gastrectomy, liver metastasis recurred and nivolumab was administered. Subsequently, liver metastases disappeared. At 55 months after gastrectomy, rectal resection was performed against rectal cancer and partial liver resection against liver metastases. Cancer cells were not detected in the resected specimens.

[A Case Report of Recurrent Bleeding and Massive Malodorous Effusion Due to Skin Invasion of Advanced Breast Cancer Successfully Treated with Mohs' Paste].

We report a case involving a 65-year-old woman with skin invasion and destruction by left large breast cancer(T4cN0M0, Stage ⅢB). She had severe anemia with recurrent bleeding on the cancer surface and needed blood transfusion, and massive malodorous effusion from the skin lesion resulted in hypoalbuminemia and recurrent bacteremia. Metronidazole gel treatment for malodorous effusion and postmenopausal hormonal therapy were administered at first. After using Mohs' paste 4 times with 1- or 2-week intervals, the bleeding and effusion stopped, and the primary cancer tumor almost disappeared. Bacteremia also improved with antibiotics, and amelioration of distress was observed. Following this, systemic chemotherapy was performed. Mohs' paste was a very useful method for symptom management of malignant skin lesions with bleeding and massive effusion.

[A Case of Unresectable Pancreas Cancer with 32 Months Survival after Chemotherapy].

We report a case of unresectable pancreas cancer. A 70-year-old woman presented with worsening diabetes and serum CA19-9 elevation. A tumor with portal vein and supra-mesenteric vein invasion was observed by computed tomography. She was diagnosed with unresectable pancreas head cancer that was locally advanced. Chemotherapy was administered with gemcitabine and nab-paclitaxel for 19 courses, followed by gemcitabine alone for 4 courses. After the addition of 6 courses of chemotherapy, a 60%dose of chemotherapy was administered for 13 courses due to severe neutropenia. The patient died 32 months after the first visit. The 60% dose of gemcitabine and nab-paclitaxel also inhibited tumor growth. These findings suggest the effective and safe long-term use of gemcitabine and nab-paclitaxel.

[A Case Report of Continuous Bleeding due to Severe Skin Metastases of Breast Cancer Successfully Treated Using Mohs Paste].

We report a case of severe skin metastases of advanced right breast cancer in an 84-year-old woman. The tumor (T4bN3cM0, Stage III C)was resected in June 2011(BT+AX)after blood transfusion for severe anemia. Radiotherapy to the right chest wall and supraclavicular lymph nodes was performed, and adjuvant hormonal therapy was administered. Local recurrences in the skin of the right chest wall appeared and were resected in December 2011. Nine months later, continuous bleeding from the progressed, widespread skin metastases needed recurrent blood transfusion. After using Mohs paste twice, the bleeding stopped almost completely. Mohs paste was very useful for stopping bleeding in locally advanced, unresectable skin metastasis.

ß-Shaped intracorporeal Roux-en-Y reconstruction after totally laparoscopic distal gastrectomy.

BACKGROUND: The use of laparoscopic gastrectomy for the treatment of gastric cancer has been increasing. Roux-en-Y (R-Y) reconstruction after laparoscopy-assisted distal gastrectomy is now widely used to decrease leakage and prevent reflux. Owing to the need for a less invasive technique, we have developed a new technique for intracorporeal R-Y reconstruction (ß reconstruction) after totally laparoscopic distal gastrectomy (TLDG). METHODS: In this report, we describe the ß reconstruction technique and short-term outcomes of the initial 105 patients who underwent ß reconstruction from December 2008 to March 2012. RESULTS: The operative and ß reconstruction times were 330 ± 61.3 and 29 ± 5.6 min (mean ± SD), respectively. Anastomotic leakage after gastrojejunostomy occurred in one patient (0.9 %), requiring reoperation. Four cases (3.8 %) of anastomotic stenosis required endoscopic balloon dilation. However, R-Y stasis was not noted. CONCLUSIONS: We have indicated a technical description as well as the usefulness of ß-shaped intracorporeal R-Y reconstruction after TLDG.

Petersen's hernia after laparoscopic distal gastrectomy with Roux-en-Y reconstruction for gastric cancer.

BACKGROUND: To decrease the incidence of internal hernia after laparoscopic Roux-en-Y gastric bypass, recent recommendations indicated closure of mesenteric defects and Petersen's defect. Laparoscopic distal gastrectomy for gastric cancer is used increasingly, so the incidence of Petersen's hernia can also increase, but the trend has not been studied. METHODS: This study retrospectively reviewed 358 consecutive patients who underwent laparoscopic distal gastrectomy for gastric cancer at one institution, with antecolic Roux-en-Y (RY) reconstruction. RESULTS: Petersen's hernia occurred in 6 (2.2 %) of 268 patients whose Petersen's defect was not closed by a mean of 351 days after surgery. All the patients underwent reoperation with reduction and repair of the hernia except the first case. In 90 subsequent cases, with closure of the Petersen's defect, internal hernias did not occur (0/90 cases; p = 0.06). Focusing on the totally laparoscopic procedure, Petersen's hernia occurred in 2 (5.1 %) of 39 patients, whereas in 81 subsequent cases, with closure of Petersen's defect, internal hernias did not occur (0/81 cases; p = 0.03). CONCLUSIONS: Based on the recent recommendations for bariatric surgery, closure of this potential hernia defect is necessary after laparoscopic distal gastrectomy with R-Y reconstruction for gastric cancer.

[A case of locally recurrent breast cancer difficult to differentiate from nodular fasciitis].

Breast-conserving surgery was performed on a 78-year-old woman for left breast cancer 5 years previously (invasive ductal carcinoma, T1cN2M0, stage IIIA, ER[+], PR[-], HER2[-]). Chemotherapy, radiotherapy, and hormonal therapy were administered. A left subclavian tumor was detected, and an excisional biopsy was performed. Histological examination showed spindle cells, different from primary breast cancer histology, and nodular fasciitis was diagnosed negative cytokeratin and vimentin immunostaining results. After 12 months, a mass had developed in the same region, and reoperation was performed for resection. Similar spindle cells were observed, but they tested positive for cytokeratin. Carcinoma was diagnosed and thought to be locally recurrent breast cancer. Despite postoperative chemotherapy, the patient experienced bone and lung metastasis and a third local recurrence. She died 13 months following the last surgery. Recurrent breast cancer sometimes displays different histology from the initial cancer, and mimics stromal tumors in certain cases.

Clinical outcomes of laparoscopy-assisted gastrectomy for patients with heart disease.

Laparoscopy-assisted gastrectomy (LG) is an established treatment for early gastric cancer. However, CO2 pneumoperitoneum during laparoscopic surgery can adversely affect cardiac function in the presence of heart disease (HD). We performed LG in 546 patients and conventional open gastrectomy (OG) in 448 patients. Patients with preoperatively diagnosed and treated HD were identified. The clinical outcomes of patients with HD who underwent LG (HD-LG) were compared with those of patients with HD who underwent OG (HD-OG), as well as those of patients with no operative risk who underwent LG (NR-LG). Variables of cardiac function were similar in the HD-LG and HD-OG groups. Postoperative cardiac complications did not differ between the groups (8.3% vs. 13.6%, P = 0.51). The HD-LG group had significantly more cardiac and abdominal complications than the NR-LG group (P = 0.0011 and 0.0070, respectively). LG was tolerated in patients with gastric cancer and mild or moderate HD, similar to OG.

Feasibility of laparoscopy-assisted gastrectomy for patients with chronic obstructive pulmonary disease.

BACKGROUND: Laparoscopy-assisted gastrectomy (LG) is an established treatment for early gastric cancer. However, carbon dioxide pneumoperitoneum during laparoscopic surgery can adversely affect the pulmonary function of patients with chronic obstructive pulmonary disease (COPD). This retrospective cohort study was performed to assess the feasibility of LG for patients with COPD. METHODS: Among 1,053 patients who underwent radical gastrectomy with lymph node dissection between 1999 and 2011 at the authors' hospital, 220 patients with COPD were studied retrospectively. The clinical outcomes for the patients with COPD who underwent LG (LG group) were compared with those of COPD patients who underwent open gastrectomy (OG group), as well as those of patients with no operative risk and normal pulmonary function who underwent LG (NOR group). Postoperative pulmonary complications (PPCs) were defined as pneumonia, atelectasis, pneumothorax, prolonged mechanical ventilation (>24 h), and adult respiratory distress syndrome within 30 days after operation. RESULTS: Pulmonary function variables were similar in the LG and OG groups. The findings showed PPCs to be slightly but not significantly less frequent in the LG group (1.7 %) than in the OG group (6.3 %) (p = 0.09). No difference in PPCs was found between the LG group and the NOR group (p > 0.99). For patients with COPD, advanced stage (stage 2 or 3 vs stage 1) was significantly associated with PPCs (p = 0.03), but was not an independent risk factor for PPCs (p = 0.12). CONCLUSION: The LG procedure is tolerated in patients with gastric cancer who have mild or moderate COPD, similar to OG.

Long-term outcomes of Roux-en-Y and Billroth-I reconstruction after laparoscopic distal gastrectomy.

BACKGROUND: Laparoscopic distal gastrectomy (LDG) is an established procedure for the treatment of early gastric cancer. Roux-en-Y (R-Y) or Billroth-I (B-I) reconstruction is generally performed after LDG in Japan. The aim of this retrospective cohort study was to compare the effectiveness of R-Y and B-I reconstructions and thereby determine which has better clinical outcomes. METHODS: We analyzed data from 172 patients with gastric cancer who underwent LDG. Reconstruction was done by R-Y in 83 patients and B-I in 89. All patients were followed up for 5 years. Evaluated variables included symptoms, nutritional status, endoscopic findings, gallstone formation, and later gastrointestinal complications. RESULTS: Scores for the amount of residue in the gastric stump, remnant gastritis, and bile reflux, calculated according to the "residue, gastritis, bile" scoring system, were significantly lower in the R-Y group (score 0 vs. 1 and more; p = 0.027, <0.001, and <0.001, respectively). The proportion of patients with reflux esophagitis was significantly lower in the R-Y group (p < 0.001). Relative values (postoperative 5 years/preoperative) for body weight, serum albumin level, and total cholesterol level were similar in the two groups (p = 0.59, 0.56, and 0.34, respectively). Gallstone formation did not differ between the groups (p = 0.57). As for later complications, the incidence of gastrointestinal ulcer was 4.5 % in the B-I group, and that of ileus was 3.6 % in the R-Y group, but differences between the groups were not significant (p = 0.12, 0.11, respectively). CONCLUSIONS: As compared with B-I, R-Y was associated with lower long-term incidences of both bile reflux into the gastric remnant and reflux esophagitis.

[Pancreatoduodenectomy for locally advanced ascending colon cancer after neoadjuvant chemotherapy (mFOLFOX6)].

A 69-year-old man was referred to our hospital with the chief complaint of a palpable abdominal mass. Computed tomography and colonofiberscopy revealed that a large type 2 ascending colon cancer had invaded the duodenum and pancreas. To down-size the tumor, chemotherapy was planned and a FOLFOX regimen was effective; we therefore decided to perform a radical operation. The patient is still alive and disease-free 1 year and 8 months after the surgery.

Clinicopathological and prognostic significance of PDCD4 and microRNA-21 in human gastric cancer.

Recent studies have demonstrated that the novel tumor suppressor protein programmed cell death 4 (PDCD4) is downregulated in several human solid cancer types and is suppressed by microRNA-21 (miR-21). The objectives of this study were: i) to establish the clinicopathological and prognostic significance of PDCD4 mRNA, and ii) to elucidate any correlation between PDCD4 mRNA and miR-21 in gastric cancer. The expression status of PDCD4 mRNA was investigated by qRT-PCR and protein expression was analyzed by an immunohistochemical study. We analyzed PDCD4 mRNA expression with respect to various clinicopathological factors in 105 gastric cancers. We also performed an association study comparing PDCD4 mRNA and miR-21 in eight cell lines and 49 gastric cancers. Expression of PDCD4 mRNA in cancer tissues was significantly lower than in non-cancer tissues (P<0.05). Patients with low PDCD4 mRNA expression was significantly correlated with size, depth, lymph node metastasis, venous invasion, advanced stage, and poor clinical prognosis (P<0.05). Expression of miR-21 in cancer tissues was significantly higher than in non-cancer tissues (P<0.05). Elevated miR-21 expression was significantly correlated with size and depth (P<0.05). An inverse correlation between PDCD4 mRNA and miR-21 was found in gastric cancer. This study revealed that low PDCD4 expression correlates with biological aggressiveness and poor prognosis in gastric cancer. Furthermore, our findings suggest that PDCD4 mRNA is negatively regulated by miR-21 in gastric cancer and may serve as a target for effective therapies.

Over- and under-expressed microRNAs in human colorectal cancer.

MicroRNAs (miRNAs) constitute a class of small (21-23 nucleotides) noncoding RNAs that function as post-transcriptional gene regulators. It is becoming increasingly clear that altered miRNA expression correlates with the pathogenesis of cancers. The purpose of this study was to determine the up-regulated miRNAs in human colorectal cancer. Total RNA was isolated from cancer tissues and corresponding noncancerous tissues from surgically resected colorectal cancers. The expression profiles of miRNAs were determined using a miRNA microarray containing 455 human miRNA probes. The expression status of selected miRNAs in paired clinical samples was then investigated by real-time RT-PCR. Twenty-one miRNAs were identified by miRNA array analysis as overexpressed in colorectal cancer tissues compared to normal epithelial tissues. Among them, the expression of miR-31, miR-183, miR-17-5p, miR-18a, miR-20a and miR-92 were confirmed to be significantly higher in cancer tissues than in normal tissues (P<0.05). In contrast, the expression of miR-143 and miR-145 in cancer tissues were significantly lower than in normal tissues (P<0.05). The miR-18a overexpression group tended to have a poorer clinical prognosis than the low expression group (P=0.07). We identified miRNAs that were overexpressed or under-expressed in colorectal cancers and which may be correlated with colorectal carcinogenesis.

Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family.

PURPOSE: The high mobility group A2 (HMGA2) nonhistone chromosomal protein can modulate transcription by altering chromatin architecture. HMGA2 is highly expressed during embryogenesis and in various benign and malignant tumors. Recent studies report that HMGA2 is negatively regulated by the let-7 microRNA (miRNA) family. However, no studies have examined the clinical significance of HMGA2 and its relationship to the let-7 miRNA family in gastric cancer. EXPERIMENTAL DESIGN: Using quantitative real-time reverse transcription-PCR, we analyzed HMGA2 expression with respect to various clinicopathologic factors in 110 patients with gastric cancer. We also did an association study comparing HMGA2 expression and let-7 miRNA family expression in gastric cancer. RESULTS: Expression of HMGA2 in cancerous tissues was significantly higher than in noncancerous tissues (P < 0.05). Elevated HMGA2 expression was significantly correlated with serosal invasion (P < 0.05) and poor clinical prognosis (P < 0.05). A multivariate analysis showed that HMGA2 expression status was an independent prognostic factor (P < 0.05). An inverse correlation between HMGA2 and let-7a was found in gastric cancer cell lines (P = 0.08). The expressions of let-7a, let-7b, and let-7c in gastric cancer patients with low HMGA2 expression were significantly higher than those with high HMGA2 expression (P < 0.05). CONCLUSIONS: High expression of HMGA2 in gastric cancer correlates with tumor invasiveness and is an independent prognostic factor. Furthermore, our findings suggest that HMGA2 is negatively regulated by the let-7 miRNA family in human gastric cancer.

Clinical significance of BMP7 in human colorectal cancer.

BACKGROUND: Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor (TGF)-beta superfamily. Recent studies demonstrated that the expression patterns of BMPs are altered in several tumors. The purpose of the current study was to examine the expression of BMP7 in malignant and normal colorectal tissues, and to analyze whether BMP7 expression levels correlate with clinicopathological variables and prognosis in colorectal cancer. METHODS: Paired colorectal tissue samples from cancer and corresponding nonmalignant tissues were obtained from 65 patients who underwent surgical resection for colorectal cancer. The expression status of BMP7 mRNA was investigated by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and protein expression was analyzed by an immunohistochemical study. RESULTS: Quantitative real-time RT-PCR showed that BMP7 mRNA expression in cancerous tissue was significantly higher than that in normal tissue (p < 0.0001). An immunohistochemical study revealed that BMP7 was predominantly expressed in cancer cells. Elevated BMP7 expression was significantly correlated with depth of tumor invasion, liver metastasis, liver recurrence, advanced Dukes' classification, and cancer-related death (p < 0.05, 0.001, 0.01, 0.05 and 0.01, respectively). Furthermore, patients with the highest levels of BMP7 expression showed the poorest prognosis (p < 0.01). A multivariate analysis showed that BMP7 expression status was an independent prognostic factor of overall survival (relative risk, 2.29; 95% confidence interval, 1.08-5.30; p < 0.05). CONCLUSIONS: Expression of BMP7 in colorectal tumors correlates with parameters of pathological aggressiveness such as liver metastasis and poor prognosis. Thus, BMP7 could be a useful clinical marker for colorectal cancer patients.