Staged Prosthetic Reconstruction with Fat Grafting for Severe Depressive Breast Deformation after Breast-conserving Therapy.

Breast-conserving therapy, where radiotherapy is performed after partial mastectomy, is a widely used surgical method that can preserve most of the breast tissue without increasing the recurrence rate of breast cancer. However, without reconstruction, asymmetry of the breast occurs due to the tissue defect and radiation fibrosis, producing in poor cosmetic results. In this case study, we performed staged prosthetic breast reconstruction combined with fat grafting for severe depressive deformation of the breast after breast-conserving therapy. The first surgery involved insertion of a tissue expander and fat grafting, second surgery was the reduction of injected saline volume and fat grafting, and third surgery involved exchange for an implant and fat grafting. The skin in the depressed area, which had atrophied, became soft and flexible; deformation was also improved, and the patient was satisfied with the aesthetic outcome. It is expected that fat grafting will fertilize and qualitatively improve the damaged tissue due to irradiation, reducing the complications related to the tissue expander and implant. We believe that it will be possible to correct a breast deformity after breast-conserving therapy using a tissue expander and implant, which had not been considered as a solution. The results showed that the present method can be an option for delayed reconstruction after breast-conserving therapy.

Vertical breast measurement in East Asian women: A guide for mastopexy and reduction to form nonptotic breasts in unilateral prosthetic breast reconstruction.

BACKGROUND: Following unilateral breast cancer surgery, mastopexy and reduction of the unaffected breast are often performed to obtain symmetrical breasts. The use of implants in breast reconstruction results in a nonptotic breast. To achieve symmetry following the procedure, the unaffected side should be nonptotic too. However, no study has yet reported any indices for the design of mastopexy and reduction in this direction. We present a new method of preoperative design that uses vertical breast measurements to form nonptotic breasts according to individual breast shapes. METHODS: We performed vertical breast measurements of the unaffected breasts of 193 patients scheduled to undergo surgery for unilateral breast cancer. The vertical base dimension (VBD) and vertical surface dimension (VSD) of the ptotic and nonptotic breasts and the height of the nipple in the nonptotic breast were measured in centimeters. RESULTS: The borderline between ptotic and nonptotic breasts was expressed using the formula VSD = 1.13 × VBD + 1.86. The height of the nipple in nonptotic breasts was 0.8 times the distance between the sternal notch and lowest point of the inframammary fold on the midline. From these findings, we formulated a new method for forming a nonptotic breast from a ptotic breast using an inverted T design. CONCLUSION: These results can be used for the design of mastopexy and reduction when forming a nonptotic breast on the unaffected side. These procedures can be performed without significantly lifting the nipple-areolar complex if required during unilateral prosthetic breast reconstruction.

[Analysis of Esophageal Cancer Patients Undergoing Non-Curative Resection].

The prognosis of esophageal cancer patients who undergo non-curative resection is very poor. Here, we retrospectively analyzed the factors associated with non-curative resection. Thirty-five patients with cT3 or T4 thoracic esophageal cancer treated with neoadjuvant chemotherapy or chemoradiotherapy followed by esophageal resection were included in this study. Among the 35 patients, 27 underwent curative resection (R0 group), while 8 underwent non-curative resection (R1R2 group). A comparison of the clinicopathological factors between groups revealed no significant differences in presurgical factors. The pathological T factor was significantly deeper in the R1R2 group than in the R0 group (p=0.0086). Histopathological response tended to be higher in the R0 group (p=0.055). An accurate preoperative diagnosis of T factor is important.

[Chemotherapy for gastric cancer patients over 75 years of age].

PURPOSE: The efficacy of chemotherapy for advanced or recurrent gastric cancer in patients who were aged over 75 years was investigated. MATERIALS AND METHODS: Progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with TS-1 plus cisplatin or TS-1 in our hospital from 2009 to 2013 were determined. The patients were divided into two groups: H and L. H group patients were aged over 75 years, and L group patients were aged less than 75 years. RESULTS: Median PFS and median OS of patients in the H and L groups who received TS-1 plus cisplatin chemotherapy were not significantly different. PFS was 77[range, 13-211] days and 139[range, 53-211]days for the H and L groups, respectively(p=0.141), while OS was 523[range, 22-1,030] days and 402 [range, 322-623] days, respectively (p=0.620). Similarly, median PFS and median OS of patients who received TS-1 chemotherapy were not significantly different between the H and L groups. PFS was 103[range, 51-156]days and 152.5[range, 85-278]days for the H and L groups, respectively (p=0.230), while OS was 414 [range, 224-714]days and 605[range, 452-1,077] days, respectively ( p=0.1337). CONCLUSION: PFS and OS were not significantly different in younger patients with advanced gastric cancer who received TS-1 plus cisplatin or TS-1 chemotherapy compared to that in similarly treated elderly patients with advanced gastric cancer.

[Efficacy of capecitabine/cisplatin chemotherapy after failure of all conventional therapies in patients with advanced gastric cancer].

There is no standard therapy for advanced gastric cancer patients who had already failed treatment with major anti-cancer drugs including fluoropyrimidine, cisplatin, taxans, and irinotecan. We report the results of treatment with capecitabine and cisplatin(XP)after the failure of all other conventional therapies. A total of five advanced gastric cancer patients were treated. The median age was 59 years(range, 46-76); there were 3male and 2 female patients; performance status was 0/1/2: 2/2/ 1 patients, respectively. The median duration from start of first-line chemotherapy to XP was 653 days(range, 372-1,107). Three patients were treated after fourth-line therapy and two patients after fifth-line therapy. All of the patients had received S-1, cisplatin, irinotecan, paclitaxel, and docetaxel previously. Patients received 80mg/m2 of cisplatin intravenously on day 1, and 1,000mg/m2 of capecitabine orally twice a day from day 1 to day 14 followed by a 7-day rest period. Treatment courses were between 2 to 5. Median time to progression was 107 days. Median overall survival was 245 days. One PR and one SD were reported. All reported adverse events were manageable. XP is considered one of the effective regimens for advanced gastric cancer after all conventional therapies have failed.

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609.

PURPOSE: The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC). METHODS: Eligible patients had received one or fewer prior chemotherapy regimens for MBC. Patients received oral capecitabine of low dose (828 mg/m(2) twice daily, days 1-21) plus paclitaxel (80 mg/m(2), i.v., over 60 min, days 1, 8 and 15) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival (OS) and safety were secondary endpoints. An exploratory analysis of efficacy according to hormone receptor (HR) status was performed. RESULTS: Forty-four patients were enrolled, and 43 patients were evaluable. ORR was 46.5%. PFS and OS were 8.3 and 22.9 months, respectively. ORR was 45.5% in patients with HR-positive tumors and 50% in HR-negative cases. The most frequently observed grade 3/4 adverse events were neutropenia (27.9%), leukopenia (11.6%), hand-foot syndrome (HFS, 9.3%) and fatigue (7.0%). There were no discontinuations due to HFS. CONCLUSIONS: Monthly XP was an effective and well-tolerated regimen for the first- or second-line treatment for MBC.

[Analysis of weekly paclitaxel chemotherapy for esophageal cancer].

PURPOSE: Public knowledge-based application for paclitaxe(l PAC) has been approved for advanced or recurrent esophageal cancer. We investigated the feasibility of weekly PAC chemotherapy as a second-line or subsequent regimen for metastatic or recurrent esophageal cancer. MATERIALS AND METHODS: Patients received PAC( 100 mg/m2 intravenously) on days 1, 8, 15, 22, 29, and 36 of each 8-week period. We analyzed the toxicity and efficacy in 6 patients treated with the weekly PAC chemotherapy. RESULTS: Grade 3-4 toxicities were neutropenia, leukopenia, and anemia. Two patients had stable disease and 2 had progressive disease. CONCLUSION: By managing the side effects, weekly PAC therapy is considered a feasible regimen that can be administered on an outpatient basis.

[A case of advanced gastric cancer with para-aortic lymph node metastasis successfully treated with preoperative S-1/Lentinan chemotherapy followed by curative gastrectomy].

We report a case of advanced gastric cancer successfully treated with preoperative S-1/Lentinan (LTN)chemotherapy followed by curative gastrectomy. The patient was a 75-year-old man with right hypochondralgia. Endoscopic examination revealed a huge type 2 gastric cancer in the middle body of the stomach. Abdominal computed tomography (CT) revealed multiple perigastric lymph node metastases and bulky para-aortic lymph node metastases. The clinical diagnosis was cT 4N3M1( LYM) with cStage IV. We thought a complete resection would be difficult, so he was treated with S-1( 80 mg/m2 day 1-28/q6w) and LTN (2 mg weekly) in May 2010. After 3 courses, the primary lesion was markedly reduced, and gastric endoscopic biopsy showed no malignant lesion. After 4 courses, abdominal CT showed no lymph node swelling at the perigastric and para-aortic areas. After 5 courses, distal gastrectomy with D2 lymphadenectomy was performed. The histological diagnosis was ypT2( MP) N0M0, Stage IB. Histological features of the primary tumor and lymph nodes were judged to be Grade 2 and Grade 3, respectively. After surgery, S-1/LTN treatment was continued for 1 year. During this period, there were no serious adverse events. The patient has been in good health without recurrence for 28 months after surgery.

[A case of HER2-positive advanced gastric cancer successfully treated with a combination of capecitabine, cisplatin, and trastuzumab as first-line chemotherapy].

We report a case of human epidermal growth factor receptor(HER)2-positive advanced gastric cancer successfully treated with a combination of capecitabine, cisplatin(CDDP), and trastuzumab as first-line chemotherapy. A 66-year-old woman diagnosed as having advanced gastric cancer underwent chemotherapy after abdominal computed tomography (CT)revealed multiple metastases to the liver, lung, lymph nodes, and peritoneum. Histopathological examination indicated a type 3, tub1, cT3(SS), N3, H1, P1, M1(LYM, PUL), cStage IV gastric tumor. Because overexpression of HER2 protein was observed in primary tumor immunostaining, combination therapy of capecitabine+CDDP+trastuzumab was administered as first-line chemotherapy. After 4 courses, CT scans revealed decreased primary tumor size, liver lesion, lymph nodes, and elimination of the lung lesion, thereby suggesting a partial response(PR). The grade 3 adverse events were neutropenia, anemia, and anorexia. After discontinuation of CDDP because of elevation of serum creatinine levels, combination therapy with capecitabine and trastuzumab was continued.

[A case of paclitaxel-resistant recurrent gastric cancer responsive to S-1 plus docetaxel].

We report the case of a patient with paclitaxel (PTX) -resistant recurrent gastric cancer who was effectively treated with S-1 plus docetaxel( DOC). A 62-year-old woman underwent total gastrectomy for Stage IV advanced gastric cancer (type 4, por 2>sig, pT4a (SE), pN3a, pP1, CY1) in 2009. Although S-1 was administered as first-line chemotherapy, recurrent peritoneal metastasis was diagnosed 22 months after surgery. S-1 plus irinotecan (CPT-11) was administered as second-line chemotherapy, and this was followed by weekly PTX (80 mg/m2) as third-line chemotherapy. However, computed tomography (CT) showed increased ascites and peritoneal wall thickening in the pelvis. As the tumor proved resistant to PTX, making the treatment ineffective, S-1( 80 mg/m2, day 1-14, q3w) plus DOC( 40 mg/m2, day 1, q3w) was initiated. Two months later, the ascites and peritoneal wall thickening in the pelvis disappeared. Twelve months after initiation of S-1 plus DOC chemotherapy, no sign of recurrence has been noted.

[Analysis of patients with gastrointestinal neuroendocrine tumor].

PURPOSE: We investigated the background factors, histopathological results, and prognosis of patients with gastrointestinal neuroendocrine tumors. MATERIALS AND METHODS: The medical records of 42 patients with gastrointestinal neuroendocrine tumors who were diagnosed and treated at our hospital from 2002 to 2012 were collected and retrospectively reviewed. RESULT: The ratio of male to female patients was 29:13; the mean age was 66.1 years. The tumors were located in the esophagus( 2 patients), stomach( 13 patients), duodenum( 9 patients), colon( 1 patient), and rectum( 18 patients). Regarding the depth of the tumor, invasion of the submucosa( SM) was observed in 26 patients; invasion of the muscularis propria( MP), in 1 patient; invasion of the subserosa( SS), in 3 patients; penetration of the serosa( SE)( AD), in 1 patient, invasion of the adjacent structures( SI)( AI), in 3 patients; and the extent of tumor invasion was unknown in 1 patient. Patients who experienced relapse had a poor prognosis, and all the patients died.

[Analysis of combination chemotherapy with docetaxel and nedaplatin for esophageal cancer].

PURPOSE: There is no standard second line regimen for metastatic or recurrent esophageal cancer. We investigated the feasibility of combination chemotherapy with Docetaxel (DOC) and Nedaplatin (CDGP) as a second-line regimen for metastatic or recurrent esophageal cancer. MATERIALS AND METHODS: Patients received DOC (60 mg/m2 intravenously) on day 1 and subsequently CDGP(70 mg/m2 intravenously) on day 1 of each 4-week period thereafter. We analyzed the toxicity and efficacy in 9 patients treated with combination chemotherapy with DOC and CDGP. RESULT: The observed Grade 3-4 toxicities were neutropenia and anemia. Three patients had stable disease and 6 patients had progressive disease. The median progression free survival and overall survival were 4.3 and 8.1 months, respectively. CONCLUSION: Combination chemotherapy with DOC and CDGP is considered a feasible second line regimen for metastatic or recurrent esophageal cancer.

p53 inhibits vascular endothelial growth factor expression in solid tumor.

BACKGROUND: The p53 tumor-suppressor gene is one of the most frequently mutated genes in cancers, and its mutations affect various biological actions, such as tumor growth, apoptosis, and so on. During hypoxia, p53 is stabilized by interaction with hypoxia-inducible factor-1 (HIF-1). This interaction raised the possibility for regulating HIF-1 activity by p53, which is still to be elucidated. METHODS: First, we introduced various types of the p53 mutant gene into Hep3B and evaluated the role of p53 in hypoxic responses, including vascular endothelial growth factor (VEGF) production and HIF-1 activation. Second, Hep3B-vector cells and Hep3B-p53 cells were subcutaneously injected into BALB/c (nu/nu) mice, and tumor progression and the hypoxic responses were analyzed. Finally, we investigated the role of the p53 mutant genes in the level of vascularity in human pancreatic neoplasia. RESULTS: Here, we showed that expression of wild-type p53, but not null or mutated p53, significantly suppressed HIF-1 activity and production of VEGF, which mostly depends on the HIF-1ß protein level. In a tumor xenograft model, we consistently found that loss of p53 promotes VEGF production, neovascularization, and tumor progression via accumulation of HIF-1ß protein. Furthermore, in clinical pancreatic neoplasia, tumors with mutated p53 have significantly higher levels of vascularity than those with wild-type p53. CONCLUSION: These results indicate that loss of p53 contributes to neovascularization through regulation of HIF-1.

[Two cases of HER2-positive advanced or metastatic breast cancer, responding to lapatinib and capecitabine].

The first patient was a 59-year-old woman who was diagnosed with invasive scirrhous carcinoma. The tumor was estrogen receptor (ER)-positive, progesterone receptor (PgR)-positive, and human epidermal growth factor receptor 2 (HER2)-positive. The patient was treated with adjuvant chemotherapy and endocrine therapy after surgery. Liver metastases developed 5 years after surgery. She was treated with trastuzumab combined with vinorelbine, paclitaxel, or docetaxel. The liver metastases increased in size, 9 years after surgery, and she was treated with lapatinib and capecitabine. The efficacy of chemotherapy was judged as a partial response. The second patient was a 74-year-old woman who was diagnosed with invasive ductal carcinoma in 2005. The tumor was ER-negative, PgR-positive, and HER2-positive; she was treated with trastuzumab and paclitaxel. She developed dyspnea in January 2010. Chest radiograph showed increased lung metastases and left pleural effusion; she was treated with lapatinib and capecitabine. Lung metastases decreased and left pleural effusion disappeared after the first cycle of chemotherapy. The efficacy of chemotherapy was judged as a partial response.

Primary colorectal signet-ring cell carcinoma: clinicopathological features and postoperative survival.

PURPOSE: The objective of this study was to investigate the clinicopathological features and postoperative survival of primary colorectal signet-ring cell carcinoma. METHODS: Nineteen patients with primary colorectal signet-ring cell carcinoma were identified from a database of 5884 surgical patients with colorectal cancers treated surgically at Osaka University Hospital and affiliated hospitals between 1993 and 2007. The clinicopathological data of those patients were compared with those of 5792 patients with non-signet-ring cell colorectal carcinoma (5417 with well or moderately differentiated adenocarcinoma and 375 with poorly differentiated adenocarcinoma or mucinous carcinoma). RESULTS: All patients showed a tumor depth of over T3. Lymph node involvement occurred in 14 patients. Seven of 19 patients presented with distant metastasis at the time of diagnosis. The overall 5-year survival rate in primary signet-ring cell carcinoma was significantly lower at 24.1%, in comparison to 77.5% in well or moderately differentiated adenocarcinoma and 57.7% in poorly differentiated adenocarcinoma or mucinous carcinoma. Likewise, the postoperative survival in Stage III was also significantly worse. On the other hand, no significant difference was observed in Stage II or IV. CONCLUSION: The most important feature of primary colorectal signet-ring cell carcinoma is the advanced stage at the time of diagnosis. In addition, the postoperative survival is worse than for other types of colorectal cancer.

Feasibility of end-to-anterior wall anastomosis in conversion of the double-stapling technique during laparoscopically assisted surgery.

BACKGROUND: Double stapling technique (DST) is a physiological end-to-end anastomosis that is currently used widely in rectal surgery and also in sigmoidectomy. In laparoscopy-assisted sigmoidectomy, we occasionally encounter obstruction during insertion of the circular stapler device from the anus. In such cases, we used to cut the residual rectosigmoid colon additionally and to allow DST anastomosis. Here, we propose an alternative way to overcome this difficulty, that is to perform an anastomosis to the anterior wall of the rectosigmoid colon. METHODS: Between 2001 and 2007, we experienced the cases of 10 sigmoid colon cancer patients who underwent laparoscopic surgeries with a conversion from DST to end to side (anterior wall) anastomosis. RESULTS: None of the patients suffered from anastomosis leakage, and none had complained of their stool habits. Colonoscopy showed that anastomosis window is kept wide and that stool is not pooled in the blind pocket of the rectosigmoid colon, suggesting the passage is well preserved. CONCLUSION: Our experience indicates that though several technical points should be noted, an end to anterior wall anastomosis procedure is easy and safe. This method is a useful alternative way when end-to-end DST anastomosis is not performed smoothly in laparoscopic surgery.

A case of advanced mucinous cystadenocarcinoma of the pancreas with peritoneal dissemination responding to gemcitabine.

Mucinous cystic neoplasm(MCN)of the pancreas is a rare disease. A 34-year-old female was referred to our hospital for a giant cystic tumor in the left epigastrium, suspected of being a pancreatic MCN. The surgical findings revealed that the tumor originated in the pancreatic tail with the presence of peritoneal dissemination. A distal pancreatectomy and a splenectomy were performed, and the resected specimen histologically revealed an invasive mucinous cystadenocarcinoma of the pancreas. The postoperative computed tomography(CT)scan showed metastatic tumors of the Douglas pouch and the left ovary. Gemcitabine(GEM)was thereafter systemically administered for palliative chemotherapy with a regimen of 1,000 mg/m / 2week for 3 weeks, followed by a week of rest. When assessed by a CT scan after 4 courses of chemotherapy, marked shrinkage of the tumors was identified, and we could not detect the tumors clearly. Moreover, the serum CA19-9 level fell from 341 U/mL to almost normal and there were no severe adverse events. Therefore, systemic chemotherapy with GEM is considered to possibly be an effective treatment against MCN. We describe herein the first case of advanced mucinous cystadenocarcinoma of the pancreas with peritoneal dissemination responding to GEM and a brief review of the literature.

Overexpression of eukaryotic elongation factor eEF2 in gastrointestinal cancers and its involvement in G2/M progression in the cell cycle.

A high level protein synthesis is one of the characteristics of cancer cells. The aim of this study is to show the contribution of eukaryotic elongation factor 2 (eEF2), which plays an essential role in the polypeptide chain elongation step, in the tumorigenesis of gastrointestinal cancers. In the present study, we demonstrated by using immunohistochemistry that eEF2 protein was overexpressed in 92.9% (13 of 14) of gastric and 91.7% (22 of 24) of colorectal cancers. No mutations were found in any of the exons of the eEF2 gene in six gastric and six colorectal cancers. Knockdown of eEF2 by eEF2-specific short-hairpin RNA (shEF2) inhibited cancer cell growth in two gastric cancer cell lines, AZ-521 and MKN28, and one colon cancer cell line, SW620. Flow cytometric analysis showed that knockdown of eEF2 induced G2/M arrest and resulted in inactivation of Akt and cdc2 (a G2/M regulator) and activation of eEF2 kinase (a negative regulator of eEF2) in these cancer cells. Conversely, forced expression of eEF2 in AZ-521 cells significantly enhanced the cell growth through promotion of G2/M progression in cell cycle, activated Akt and cdc2, and inactivated eEF2 kinase. Furthermore, forced expression of eEF2 in these cancer cells enhanced in vivo tumorigenicity in a mouse xenograft model. These results showed that overexpressed eEF2 in gastrointestinal cancers promoted G2/M progression and enhanced their cell growth in vitro and in vivo. These results also suggested a novel linkage between translational elongation and cell cycle mechanisms, implying that the linkage might play an important role to orchestrate the deregulated translation and cell cycle mechanisms for promotion of the development of gastrointestinal cancers.

Dacarbazine-Doxorubicin therapy ameliorated an extremely aggressive mesenteric desmoid tumor associated with familial adenomatous polyposis: report of a case.

A 30-year-old man with familial adenomatous polyposis (FAP) underwent prophylactic proctocolectomy by laparoscopy-assisted surgery. After 10 months, we found an intra-abdominal tumor, which grew rapidly to 25 cm in diameter. We performed an emergency operation, which revealed that it was a desmoid tumor derived mainly from colorectal mesenterium. The tumor was removed with three short segments of intestine and the left ureter. A computed tomography (CT) scan done 3 months later showed a 10 cm mesenteric desmoid tumor at the beginning of jejunum, approaching the root of the superior mesenteric artery (SMA). Fortunately, we were able to remove the tumor without injuring the SMA. To our distress, however, another recurrent mesenteric desmoid tumor was discovered in the pelvis one month later, which grew rapidly from 5 cm to 16 cm within 4 months. During this period, we gave the patient several regimens, including antiestrogen (tamoxifen), a nonsteroidal anti-inflammtory drug and imatinib mesylate (Gleevec), which had little or no effect. Finally, when the desmoid occupied the pelvic space, we gave the patient dacarbazine (DTIC) and doxorubicin (DOX). After seven courses, the mesenteric tumor showed an almost complete response (CR). The chemotherapy caused grade 3 to 4 leukocytopenia, but without any hazardous events. No evidence of further recurrence of mesenteric desmoid has been seen for 4 years. This combination chemotherapy is a promising strategy, even against an extremely aggressive, life-threatening mesenteric desmoid associated with FAP.