A case of Spigelian hernia after laparoscopic incisional hernia repair.

Laparoscopic ventral hernia repair with intraperitoneal onlay mesh reinforcement is often performed in clinical practice. We herein describe a patient who developed a Spigelian hernia at the edge of the mesh due to rupture of the muscular layer in the abdominal wall. A 69-year-old woman developed a left-sided abdominal bulge 15 months after laparoscopic ventral hernia repair. CT showed a 33-mm defect in the abdominal wall at the lateral edge of the left abdominal rectus muscle with an intestinal prolapse through the defect. She was diagnosed with a Spigelian hernia and underwent operation. The hernia orifice was located at the aponeurosis of the transverse abdominal muscle where the thread had been used to fix the mesh through all layers of the abdominal wall. This report details a case of a Spigelian hernia after laparoscopic ventral hernia repair.

Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. SUMMARY OF BACKGROUND DATA: The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. METHODS: Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. RESULTS: Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. CONCLUSIONS: This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.

[Brain Metastasis and Leptomeningeal Carcinomatosis after Surgery for Esophageal Cancer-A Case Report].

A 70-year-old man had undergone thoracoscopic esophagectomy following neoadjuvant chemotherapy for thoracic esophageal squamous cell carcinoma 3 years before presentation. He was undergoing whole-brain irradiation following surgery for a solitary brain metastatic tumor. The chief complaint was left leg pain during irradiation. FDG-PET/CT and MRI revealed metastases in bilateral cauda equina S1 nerve roots. Cerebrospinal fluid examination also revealed malignant cells. He received chemotherapy with 2 courses of 5-fluorouracil and cisplatin following 30 Gy of spinal irradiation. To control neurological symptoms, 4 courses of intrathecal chemotherapy with methotrexate, cytarabine, and betamethasone were performed. However, he gradually weakened and died 8 months after brain metastasis and 7 months after leptomeningeal carcinomatosis. The multidisciplinary treatment using irradiation and systemic and intrathecal chemotherapies could improve the survival of patients with leptomeningeal carcinomatosis of esophageal squamous cell carcinoma.

[Effect of Proteinuria in Patients Receiving Anti-VEGF Therapy for Advanced Colorectal Cancer].

Grade 2 or 3 proteinuria was observed in 54 patients out of 158 metastatic colorectal cancer patients receiving anti-VEGF therapy. Patients with diabetes and hypertension were risk for severe proteinuria. ARBs were more frequently used in patients with severe proteinuria. However, they could not reduce proteinuria. The examination of protein/creatinine ratio was useful for continuing anti-VEGF therapy.

Paget's disease of the male breast: a case report.

The patient was a 91-year-old man with change in nipple appearance, itching and redness, and a palpable breast mass. At presentation, mammary Paget's disease (PD) was clinically suspected. Skin biopsy was performed and showed epidermis invaded by Paget cells, characterized by hyperchromatic nuclei and abundant pale-staining cytoplasm. Computed tomography and mammary ultrasonography confirmed the absence of an underlying invasive carcinoma, and the patient underwent right mastectomy and sentinel lymph node biopsy (SLNB). Both sentinel lymph nodes were found to be negative perioperatively, and further axillary dissection was not performed. Pathological results revealed no malignancy under the nipple, yet the Paget cells were more widely spread than expected. The patient was followed up without the need of postoperative chemotherapy. Male mammary PD is an extremely rare breast cancer, and there is no standard preoperative assessment or operative procedure. Mammography is many times unable to detect possible underlying breast carcinoma in female patients with mammary PD, and previous studies have reported that the detection rate was less than 50 %. However, some researchers reported that magnetic resonance imaging (MRI) might be more detectable to confirm the extent of the cancer. The extent of the skin change around the nipple is often different from the actual perimeter of Paget cells. In extra-mammary PD, mapping biopsy is known to be useful to determine areas free of cancer. The benefits of SLNB have also been demonstrated for the management of less invasive breast cancers, and previous reports have shown that the use of SLNB is reasonable for treatment of mammary PD without underlying invasive cancer. MRI, mapping biopsy, and SLNB are all less invasive procedures and thus may be suitable for treatment of male mammary PD.

[A case of rectal carcinoid with multiple liver, lymph nodes and bone metastases that responded to an octreotide therapy].

A 45-year-old man was admitted to our hospital with a chief complaint of anal bleeding. Colonoscopy revealed a lower rectal tumor diagnosed as rectal carcinoid on biopsy. Multiple metastatic liver tumors were found on abdominal CT scan. We performed an abdomino-perineal resection, a partial hepatectomy, and TACE. There seemed to be no apparent residues of a carcinoid tumor on abdominal CT. About one year after the first therapy, CT scan had revealed multiple metastases to the liver, lymph nodes and bones. Therefore, we started an octreotide LAR, which remarkably reduced the size of metastatic tumors. The treatment of an octreotide LAR had controlled the progression of metastatic tumors for two and half years. In this case, the effect of an octreotide LAR for recurrence of rectal carcinoid after local therapies brought good controls of symptoms and an inhibition of tumor growth for long-term.

[Preoperative chemoradiotherapy for resectable lower rectal cancer].

To suppress local recurrence and preserve sphincter function, we performed preoperative chemoradiotherapy( CRT) of rectal cancer. Sixteen patients with lower advanced rectal cancer received tegafur/uracil/calcium folinate+RT followed by curative resection with lateral lymph node dissection 2-8 weeks later. The male/female ratio was found to be 11:5 (41-75 years old) and the CRT was feasible for all patients. There were 11-PR and 5-SD according to RECIST criteria, and lower isotope accumulation was observed for all primary tumors in FDG-PET study. After CRT, all patients received R0 curative resection (11 APR, 2 LAR, 1 Hartmann and 1 ISR). On pathological study, 3 patients showed complete response. Surgical complications including pelvic infection, delayed a wound healing and deep venous thrombosis, etc. In conclusion, preoperative CRT of advanced rectal cancer could potentially be useful for local control and sphincter saving, however, it is necessary to manage specific surgical complications due to radiation.

[Successful chemoradiation therapy for local control of rectal cancer with multiple bone metastases--a case report].

A 78-year-old man was admitted to our institute with the symptom of melena. The patient was diagnosed as having advanced rectal cancer (T4N2M1) with multiple bone metastases. Chemoradiation therapy was chosen for the local control because our proposal of colostomy was rejected. Concurrent chemoradiation therapy [46 Gy/23 Fr+tegafur/uraci (l UFT 400 mg/m2)/calcium folinate (Leucovorin: LV 75 mg/body)] resulted in a good partial response and the patient became asymptomatic. UFT/LV were administrated and most of the bone metastases were diminished. After 3 years of disease remission with good quality of life, local tumor recurred with the symptoms of melena and bowel obstruction. Colostomy and additional radiotherapy were performed for the palliation. He died after 4 years from the initial treatment. In advanced rectal cancer with distant metastases, chemoradiation therapy for local control plus systemic chemotherapy could be an alternative to improve quality of life.

Resection of gallbladder cancer with hepatic metastasis after chemotherapy with gemcitabine.

A 69-year-old man diagnosed as having gallbladder cancer with liver invasion and metastasis to Couinaud's hepatic segment 8 (S8) was referred to our hospital. Because of the presence of liver metastasis, gemcitabine administration was chosen. Although gemcitabine was effective for the liver metastasis, his serum carcinoembryonic antigen (CEA) level had gradually increased after 12 cycles of gemcitabine administration. There was no distant metastasis other than the liver metastasis (manageable with gemcitabine) on detailed radiological examination. Therefore, we performed surgery for the primary lesion, after obtaining informed consent. Pathological examination demonstrated viable cancer cells with necrosis and fibrosis in the gallbladder, and fibrosis without viable cancer cells in the induration in liver S8. Gemcitabine was re-administered as postoperative adjuvant chemotherapy. Twenty months after the surgery, there was no sign of recurrence. In selected patients, gemcitabine treatment may be effective against gallbladder cancer with metastasis.

Impact of gemcitabine on the survival of patients with stage IV pancreatic cancer.

OBJECTIVES: The prognosis of patients with advanced pancreatic cancer remains very poor. This study was designed to elucidate the prognostic factors of patients with pancreatic cancer to evaluate appropriate treatment with gemcitabine. METHODS: Ninety-nine consecutive patients with stage IV pancreatic cancer were treated in the gemcitabine era at the Kobe University Hospital. Prognostic variables for survival were analyzed (sex, age, performance status, main site of the tumor, tumor size, major vessel invasion, distal metastasis, resection, gemcitabine, radiation, and pathological factors). The Cox proportional hazards model was used to determine the factors influencing the survival of patients with stage IV pancreatic cancer. RESULTS: Multivariate analysis revealed that pancreatic resection, gemcitabine, and distant metastasis significantly influenced the survival of all patients with stage IV pancreatic cancer. Pancreatic resection and gemcitabine were significant factors influencing the survival of patients with stage IVa pancreatic cancer, whereas gemcitabine was the strongest factor influencing stage IVb pancreatic cancer. CONCLUSIONS: Gemcitabine has a possible role for stage IV pancreatic cancer.

Superior anti-tumor protection and therapeutic efficacy of vaccination with allogeneic and semiallogeneic dendritic cell/tumor cell fusion hybrids for murine colon adenocarcinoma.

Cancer immunotherapy by dendritic cell (DC)/tumor cell fusion hybrids (DC/TC hybrids) has been shown to elicit potent anti-tumor effects via the induction of immune responses against multiple tumor-associated antigens. In the present study, we compared the anti-tumor effects of vaccinating Balb/c mice (H-2(d)) with CT26CL25 colon carcinoma cells that had been fused with either syngeneic DCs from Balb/c mice, allogeneic DCs from C57BL/6 mice (H-2(b)) or semiallogeneic DCs from B6D2F1 mice (H-2(b/d)). Preimmunization with either semiallogeneic or allogeneic DC/TC hybrids induced complete protection from tumor challenge, whereas mice preimmunized with syngeneic DC/TC hybrids were only partially protected (75% tumor rejection). The average number of pulmonary metastases after intravenous tumor injection decreased significantly following immunization with semiallogeneic or allogeneic DC/TC hybrids (8.3 +/- 7.9 or 16.3 +/- 3.5, mean +/- SD) relative to syngeneic DC/TC hybrids (67.8 +/- 6.3). These data demonstrate that vaccination with semiallogeneic DC/TC hybrids resulted in the greatest anti-tumor efficacy. Anti-tumor effects showed by in vivo studies were virtually accomplished by the frequency of induced CTLs specific to both gp70 and beta-galactosidase assessed by using pentameric assay. Among the fusion vaccines tested, semiallogeneic DC/TC hybrids induced the highest ratio of Th1 cytokine IFN-gamma to Th2 cytokine IL-10. In addition, allogeneic or semiallogeneic DC/TC hybrids elicited a significantly stronger NK activity than syngeneic DC/TC hybrids. These findings suggest that in clinical settings, DCs derived from a healthy donor (which are generally characterized as more semiallogeneic than allogeneic) may be more capable than autologous DCs of inducing promising anti-tumor effects in vaccinations with DC/TC hybrids.

Dendritic cell-tumor cell hybrids enhance the induction of cytotoxic T lymphocytes against murine colon cancer: a comparative analysis of antigen loading methods for the vaccination of immunotherapeutic dendritic cells.

Dendritic cells (DCs) have been used successfully for inducing effective anti-tumor immune responses in advanced cancer patients undergoing tumor-specific immunotherapy. Appropriate antigen pulsing is a crucial parameter for optimizing the efficacy of immunotherapy as well as anti-tumor protection therapy. Using a murine colon cancer model, we evaluated the anti-tumor efficacy of four different preparations of DC vaccines that contained either a whole tumor or its derivatives, including i) DCs pulsed with tumor lysate, ii) DCs pulsed with necrotic tumor cells, iii) DCs pulsed with apoptotic tumor cells, and iv) DC-tumor cell fusion hybrids. Our data show that DC-tumor cell fusion hybrids and DCs pulsed with irradiated apoptotic tumor cells were more potent than DCs with freeze-thawed necrotic tumor cells for the induction of protective anti-tumor responses. The vaccination of DCs pulsed with tumor lysate failed to elicit any anti-tumor effect. In animals administered with higher doses of a tumor-cell challenge, DC-tumor cell fusion hybrids elicited the most effective anti-tumor response. Among the preparations tested, mice immunized with DC-tumor cell fusion hybrids resulted in the greatest induction of cytotoxicity as measured by the cytotoxic T lymphocyte activity of both the splenocytes and the Thy1.2-positive T lymphocytes. Furthermore, the in vitro production of IFN-gamma polarized to the Th1 cytokine responses was highest in the splenocytes derived from mice vaccinated with DC-tumor cell fusion hybrids. Our results suggest that DC-tumor cell fusion hybrids are more potent inducers of protection against solid tumors, such as colon cancer, than other antigen-loading strategies using whole tumor cell materials.

[A case of unknown primary cancer responding to TS-1].

A 65-year-old male showed elevated tumor marker and intra-abdominal lymph node (LN) swelling. PET revealed an accumulation of FDG at para-aortic LNs from the mediastinum to the inguinal region. Although many different examinations were performed to detect primary cancer, none was found. We diagnosed unknown primary cancer (UPC), and administered TS-1 (100 mg/day). Six months later, the tumor marker lowered and the LN swelling reduced. PET showed a little accumulation of FDG at intra-abdominal LN. An intra-abdominal LN biopsy was performed, and an adenocarcinoma was seen at a lymph vessel. Then, 15 months later, brain metastasis was recognized and 18 months later the patient died of systematic metastasis. Autopsy was not performed, and primary cancer was not seen till the end. TS-1 proved effective for the UPC.

Correlation between expression of major histocompatibility complex class I and that of antigen presenting machineries in carcinoma cell lines of the pancreas, biliary tract and colon.

To elicit a tumor immune response, tumor antigens represented by major histocompatibility (MHC) class I complex on the cell surface is indispensable. Some investigators demonstrated that many cancer cells reduce expression of beta2-microglobulin, a transporter of antigen presenting (TAP) or low molecular protein (LMP), due to the deletion mutant or point mutation. We investigated gene expression levels of antigen presenting machineries in 13 cell lines of the pancreas, biliary tract and colon cancer by using real-time quantitative PCR. We also evaluated the correlation between expression of MHC class I and that of antigen-processing molecules in these gastrointestinal cancer cell lines. Flow cytometric analysis showed that expression of MHC class I for the pancreatic cancer cell lines was generally lower than that for the biliary tract or colon cancer cell lines. It was further found that the colon cancer cell lines HCT-15/DLD-1 showed no MHC class I expression and lack of protein expression for beta2-microglobulin. Transfection of the wild-type beta2-microglobulin gene restored MHC class I antigen expression on the cell surface for DLD-1. Quantitative real-time PCR demonstrated lower expression for TAP1, TAP2, LMP2 and LMP7 gene in five cancer cell lines. Partial correlation analysis demonstrated that LMP2 was the only antigen presenting machinery which was significantly associated with MHC class I expression. Our results suggest that beta2-microglobulin and LMP2 are important for the expression of MHC class I in 13 gastrointestinal cancer cell lines, while the combined but complex expression of antigen presenting mechanisms was related to MHC class I expression level on the surface of cancer cells.