Laparoscopic totally extraperitoneal repair for recurrent inguinal bladder hernia: A case report.

We present a case of a recurrent inguinal bladder hernia that was previously unsuccessfully operated on three times and was repaired using totally extraperitoneal repair (TEP). A 79-year-old man presented with a right inguinal swelling that had been treated three times on the same side with anterior approaches. Computed tomography confirmed a recurrent inguinal bladder hernia. TEP was performed after identifying the bladder hernia preoperatively, with previous surgeries that used a plug-and-patch technique through an anterior approach. The extraperitoneal approach allowed the bladder to be reduced without injury and the hernia to be safely repaired using a 3D Max® Light Mesh. The postoperative recovery was uneventful, with no recurrence after 1 year. TEP facilitates the diagnosis and repair of bladder hernias, emphasizing the importance of preoperative diagnosis and the efficacy of endoscopic procedures in bladder hernia repair, even in recurrent cases.

Laparoscopic Repair Following a Delayed Presentation of Traumatic Diaphragmatic Hernia: A Case Report.

Traumatic diaphragmatic hernia is a rare condition that occurs after trauma, and some patients have a delayed presentation. A laparoscopic approach is rarely used to repair traumatic diaphragmatic hernias. We encountered a case of asymptomatic diaphragmatic hernia diagnosed after a comprehensive medical examination. A 71-year-old woman was diagnosed with a delayed presentation of traumatic diaphragmatic hernia with prolapse of the greater omentum owing to a traffic injury 20 years ago. Surgery was performed laparoscopically using three ports, and intraoperative respiratory management was performed using a double-lumen tube. The 2.5-cm-diameter hernial orifice was sutured under contralateral one-lung ventilation after the greater omentum was returned to the abdominal cavity. The patient's postoperative course was uneventful, and she was discharged on the third day. Intraoperative strategies such as respiratory management and the laparoscopic approach play a crucial role in ensuring favorable postoperative outcomes. The last follow-up was at six months post-operation, and the patient was doing well.

Hypoxia-Induced CD36 Expression in Gastric Cancer Cells Promotes Peritoneal Metastasis via Fatty Acid Uptake.

BACKGROUND: The lipid scavenger receptor cluster of differentiation 36 (CD36) has been shown to have a pro-metastatic function in several cancers. Adipose tissue, a favorable site for peritoneal metastasis (PM) from gastric cancer (GC), promotes this process by providing free fatty acids (FFAs); however, the role of CD36 in PM progression from GC remains to be elucidated. MATERIALS AND METHODS: We evaluated CD36 expression in the GC cells under various conditions. CD36 overexpressing (CD36OE) MKN45 cells were prepared and their migration and invasive properties were assessed. A PM mouse model was used to investigate the biological effects of palmitic acid (PA) and CD36. Furthermore, we examined the clinical role of CD36 expression in 82 human PM samples by immunohistochemical staining. RESULTS: Hypoxia markedly increased CD36 expression in GC cells. In normoxia, only CD36OE MKN45 cells treated with PA showed an increase in migration and invasion abilities. An increased expression of active Rac1 and Cdc42 was observed, which decreased following etomoxir treatment. Conversely, hypoxia increased those capacities of both vector and CD36OE MKN45 cells. In a mouse model transplanted with CD36OE MKN45 cells, more peritoneal tumors were observed in the high-fat diet group than those in the normal diet group. In clinical samples, 80% of PM lesions expressed CD36, consistent with hypoxic regions, indicating a significant association with prognosis. CONCLUSION: Our findings indicate that a hypoxia in the peritoneal cavity induces CD36 expression in GC cells, which contributes to PM through the uptake of FFAs.

Crosstalk between cancer-associated fibroblasts and immune cells in peritoneal metastasis: inhibition in the migration of M2 macrophages and mast cells by Tranilast.

BACKGROUND: The role of tumor-stroma interactions in tumor immune microenvironment (TME) is attracting attention. We have previously reported that cancer-associated fibroblasts (CAFs) contribute to the progression of peritoneal metastasis (PM) in gastric cancer (GC), and M2 macrophages and mast cells also contribute to TME of PM. To elucidate the role of CAFs in TME, we established an immunocompetent mouse PM model with fibrosis, which reflects clinical features of TME. However, the involvement of CAFs in the immunosuppressive microenvironment remains unclear. In this study, we investigated the efficacy of Tranilast at modifying this immune tolerance by suppressing CAFs. METHODS: The interaction between mouse myofibroblast cell line LmcMF and mouse GC cell line YTN16 on M2 macrophage migration was investigated, and the inhibitory effect of Tranilast was examined in vitro. Using C57BL/6J mouse PM model established using YTN16 with co-inoculation of LmcMF, TME of resected PM treated with or without Tranilast was analyzed by immunohistochemistry. RESULTS: The addition of YTN16 cell-conditioned medium to LmcMF cells enhanced CXCL12 expression and stimulated M2 macrophage migration, whereas Tranilast inhibited the migration ability of M2 macrophages by suppressing CXCL12 secretion from LmcMF. In PM model, Tranilast inhibited tumor growth and fibrosis, M2 macrophage, and mast cell infiltration and significantly promoted CD8 + lymphocyte infiltration into the tumor, leading to apoptosis of cancer cells by an immune response. CONCLUSION: Tranilast improved the immunosuppressive microenvironment by inhibiting CAF function in a mouse PM model. Tranilast is thus a promising candidate for the treatment of PM.

Nonbacterial Thrombotic Endocarditis Associated with Acute Promyelocytic Leukemia: An Autopsy Case Report.

Valve vegetation is one of the most fearful findings for physicians. The first diagnosis that comes to their mind is infective endocarditis (IE), but it can also be noninfective; nonbacterial thrombotic endocarditis (NBTE). NBTE can be even more challenging than IE for physicians because of the wide range of differential diagnoses such as malignancies, autoimmune disorders and human immunodeficiency virus. A 45-year-old woman presented at the emergency room with a sudden onset of dysarthria and right-sided hemiplegia. Laboratory data showed her blood counts and coagulation test were mostly normal and the magnetic resonance imaging detected a high-signal-intensity change in her left brain. An echocardiogram found a vegetation-like structure on her atrial valve. We highly suspected IE leading to cerebral embolism. The clot was successfully removed by our neurosurgeons and anticoagulation therapy was started concurrently. Her state of consciousness improved, but then she suffered a brain hemorrhage and died. The autopsy revealed that the cause of her vegetation was acute promyelocytic leukemia (APL). Based on these findings, it is important to remember that APL can be the cause of NBTE even if the blood count and coagulation tests are almost normal.

Use of esophageal stent for the treatment of postoperative gastrointestinal-airway fistula after esophagectomy.

A gastrointestinal-airway fistula (GAF) after esophagectomy is a very serious postoperative complication that can cause severe respiratory complications due to digestive juice inflow. Generally, GAF is managed by invasive surgical treatment; less-invasive treatment has yet to be established. We performed esophageal stent placement (ESP) in three cases of GAF after esophagectomy. We assessed the usefulness of ESP through our clinical experience. All GAFs were successfully managed by ESP procedures. After the procedure, the stent positioning and expansion were appropriately evaluated by radiological assessments over time. The stent was removed after endoscopic confirmation of fistula closure on days 8, 23, and 71. Only one patient with a long-term indwelling stent developed a manageable secondary gastrobronchial fistula as a procedure-related complication. In conclusion, ESP was shown to be a less-invasive and effective therapeutic modality for the treatment of GAF.

Tocilizumab-resistant TAFRO Syndrome Complicated by Type II Respiratory Failure.

A 66-year-old man with a several year history of thrombocytopenia, pleural effusion and ascites, anasarca, and organomegaly presented with general fatigue, appetite loss, dyspnea with type II respiratory failure. The precise history of the patient and the re-evaluation of lymph node and bone marrow biopsies conducted by the previous physician indicated TAFRO syndrome. The patient's laboratory data improved for a year with tocilizumab, but then worsened to the point that the patient required artificial ventilation due to the deterioration of type II respiratory failure. The replacement of tocilizumab with rituximab yielded a steady improvement, but it was necessary to address the patient's persistent respiratory failure. Peripheral nerve disorder might have been involved with the patient's respiratory failure.

Thoracoscopic Surgery in a Patient with Multiple Esophageal Carcinomas after Surgery for Esophageal Achalasia.

We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a "0-IIb+IIa" lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped iodine-unstained areas, the diagnosis of which was esophageal carcinoma. Thoracoscopic subtotal esophagectomy was performed. Esophageal carcinoma may occur many years after surgery for esophageal achalasia, even if the passage symptoms have improved. So, long-term periodic follow-up is necessary for detection of carcinoma at an earlier stage.

FOLFIRI plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer: a JACCRO CC-03 multicenter phase II study.

PURPOSE: The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m², and L-leucovorin 200 mg/m² as an intravenous infusion, followed by 5-FU 400 mg/m² as an intravenous bolus and then 5-FU 2,400 mg/m² as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS). RESULTS: We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1-30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively. CONCLUSION: Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer.

[A case that showed an improved quality of life for rectal gastrointestinal stromal tumor patient treated with cytoreductive surgery].

A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.

Administration of anti-vascular endothelial growth factor antibody following hepatectomy does not inhibit remnant liver regeneration or growth of remnant metastases.

In addition to the use of chemotherapeutic agents for the prevention of multiple liver metastases from colorectal cancer, the anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab, is often used, and its effectiveness has been established. By contrast, it has been reported that the use of bevacizumab prior to or following surgery delays wound healing or liver regeneration. In this study, we investigated whether the administration of bevacizumab following hepatectomy inhibits remnant liver regeneration or the growth of remnant metastases. Mice were partially hepatectomized (31% of the liver was removed), transplanted with the murine colorectal cancer cell line, CT26, in the remnant lobe, and intraperitoneally injected with bevacizumab (4 mg/kg) for a total of 6 times. Serum VEGF levels were measured on day 1 following surgery, and each lobe of the liver was weighed on day 14. Serum VEGF levels in non-hepatectomized, tumor-bearing mice exceeded those in their non-tumor-bearing counterparts; however, the administration of bevacizumab did not reduce the serum VEGF levels. The volume of the liver lobe of the hepatectomized, CT26-transplanted and non-CT26-transplanted mice was 1,349.6 and 735.5 mg, respectively, indicating rapid growth of the CT26 transplant (p=0.023). The volume of the CT26-transplanted lobe of the bevacizumab-administered mice was 1,379.0 mg, which was not significantly different from that (1,349.6 mg) of the non-bevacizumab-administered mice. The volume of the remnant lobe of the bevacizumab-administered mice was 1,051.0 mg, which did not significantly differ from that (957.3 mg) of the non-bevacizumab-administered mice. The administration of bevacizumab following hepatectomy did not delay remnant liver regeneration, and did not suppress the growth of metastases in the remnant lobes or remnant liver regeneration.

Combination therapy of gemcitabine or oral S-1 with the anti-VEGF monoclonal antibody bevacizumab for pancreatic neuroendocrine carcinoma.

We previously reported that the administration of bevacizumab for pancreatic neuroendocrine tumors inhibited angiogenesis in the host, resulting in tumor growth inhibition. In light of these results, we compared the effect of bevacizumab/gemcitabine/S-1 combination therapy vs. bevacizumab monotherapy. The QGP-1 pancreatic neuroendocrine carcinoma cell line and the BxPC-3 ductal cell carcinoma cell line were transplanted into the subcutaneous tissue of mice, and the mice were treated for 3 weeks with bevacizumab [50 mg/kg intraperitoneally (i.p.) twice weekly], gemcitabine (240 mg/kg i.p. once weekly) and S-1 (10 mg/kg orally five times weekly). The antitumor effect and side effects were evaluated by measuring the tumor volume and weight and by changes in body weight, respectively. The tumor volume became smaller (from the maximum volume) in the group treated with bevacizumab, gemcitabine and S-1 (BGS) and the group treated with bevacizumab and gemcitabine (BG). A significant difference was noted in the tumor weight between the BG group and the group treated with bevacizumab alone. A relatively significant decrease in the body weight was observed in the BGS and BG groups. We conclude that gemcitabine is appropriate as a drug used in combination with bevacizumab for pancreatic neuroendocrine tumors.

Computed tomography virtual endoscopy with angiographic imaging for the treatment of type IV-A choledochal cyst.

Type IV-A choledochal cysts (CCs) are a congenital biliary anomaly which involve dilatation of the extrahepatic and intrahepatic bile ducts. We present the case of a 30-year-old woman with type IV-A CC, on whom three-dimensional computed tomography (3D CT) and virtual endoscopy were performed. 3D CT revealed partial dilatation in the posterior branch of the intrahepatic bile duct and a relative stricture between it and the extrahepatic bile duct. Virtual endoscopy showed that this stricture was membrane-like and separated from the surrounding blood vessels. Based on these image findings, complete cyst resection, bile duct plasty for the stricture, and hepaticojejunostomy were safely performed. To the best of our knowledge, there are no reports of imaging by virtual endoscopy of the biliary tract which show the surrounding blood vessels running along the bile duct.

Prediction of a side effect and efficacy of adjuvant chemotherapy with gemcitabine for post operative patient of pancreatic cancer by a genetic polymorphism analysis.

BACKGROUND/AIMS: Single nucleotide polymorphism (SNP) of the genes for ATP-binding cassette transporters is related to the side effects of anticancer drugs and that of drug metabolism-related enzyme genes is involved in the activation of gemcitabine (GEM). METHODOLOGY: Forty eight patients treated with adjuvant GEM chemotherapy after pancreatic cancer resection was examined for the SNP of multidrug-resistance 1 (MDR1) 2677, MDR1 3435, breast cancer resistance protein (BCRP) 421, ribonucleotide reductase M1 (RRM1)(-)524, RRM1(-)37 and deoxycytidine deaminase (CDA) 208. We divided the patients according to normal group: patients homozygous for a wild-type allele or heterozygous for a mutant allele and mutant group: those homozygous for a mutant allele. Both groups were compared regarding the outcome and the occurrence and severity of side effects. RESULTS: MDR1 2677, MDR1 3435, BCRP421, RRM1(-) 524, RRM1(-) 37 and CDA mutant groups comprised 37.5, 31.3, 0, 12.5, 4.2 and 4.2%, respectively. The occurrence of >G3 side effects was the most frequent in the MDR1 2677 mutant group at 39%. The disease-free survival and overall survival tended to be longer in the MDR1 2677 mutant group. CONCLUSIONS: A correlation between the SNP of MDR1 2677 and drug response in patients receiving GEM chemotherapy.

Single nucleotide polymorphism of multidrug-resistance 1 and anti- multidrug-resistance 1 single chain antibody treatment for the pancreatic cancer cell line.

BACKGROUND/AIMS: Anticancer drugs are essential to pancreatic cancer therapy. The multidrug-resistance 1 (MDR1) gene codes for one of the ATP binding cassette (ABC) transporters. The neutralizing antibody of MDR1 reduces the activity of MDR1 and may add to the sensitivity of anti-cancer drugs. We investigated the relationship of the single nucleotide polymorphisms (SNPs), 2677G and 3435C, in the MDR1 gene and the effect of the anti-MDR1 single chain antibody (scAb) using pancreatic cancer cell lines. METHODOLOGY: We exposed the pancreatic cancer cell lines, AsCP-1, Panc-1, BxPC-3, MIAPaCa-2 and QGP-1 to 0.1-1,000µ g/mL of 5-FU for 72h and calculated the cytotoxic reactions. Combined therapy with an established anti-MDR1 neutralizing scAb and 10µg/mL of 5-FU was also performed. RESULTS: AsCP-1 contained wild types of MDR1 2677G and 3435C, and showed the most 5-FU resistance. The anticancer effect of AsPC-1 increased with anti-MDR1 scAb, but the effect was not significant compared with other cell lines. CONCLUSIONS: The cells with the wild type SNPs of MDR1 showed drug resistance, but we were not able to confirm a remarkable effect of the anti-MDR1 antibody.

[A case of liver metastases from gastric cancer treated with stereotactic body radiation therapy].

A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.

Laparoscopic gastric pull-up and thoracoscopic esophago-esophagostomy combined with intrathoracic fundoplication for long-gap pure esophageal atresia.

The management of long-gap pure esophageal atresia (LGEA) remains controversial. An 8-month-old girl with LGEA underwent a laparoscopic and thoracoscopic gastric pull-up and esophago-esophagostomy in the right thorax combined with intrathoracic fundoplication. She was positioned supine, and three 5-mm ports were placed in the standard locations for laparoscopic Nissen fundoplication. The gastrostomy was taken down and an additional 5-mm port was inserted at the gastrostomy site. Laparoscopic gastric mobilization was performed; the short gastric and left gastric vessels were divided using harmonic shears, and the whole stomach and distal esophageal stump maintained their vascular supply via the right gastric and gastroepiploic arteries. The hiatus was enlarged by radial incisions at both cruras, and the mobilized whole stomach and distal esophageal stump were pushed up into the right thorax through the hiatus. The patient was placed in a modified prone position and three 5-mm ports were inserted into the right thorax. Via thoracoscopy, the upper esophageal pouch was dissected bluntly, and an esophago-esophagostomy was performed using interrupted 4-0 absorbable sutures and was wrapped by a 360-degree gastric fundoplication. The patient was positioned supine again, and a Heinecke-Mikulicz pyloroplasty and gastropexy were also performed laparoscopically. The patient has mild respiratory distress that requires bronchodilators; however, she is eating baby food well without vomiting. Postoperative intrathoracic gastrofiberscopy showed a well-functioning antireflux valve, and her parents are also satisfied with the cosmetic appearance of the seven small wounds. Our new procedure is feasible and is an excellent option in selected patients with LGEA.

Reconsideration of laparoscopic cholecystectomy.

We describe the surgical method of cases showing a distended gallbladder. Because the most important thing does not cause biliary tract injury, it is to find orientation carefully. The frequency of incidental gallbladder cancer was in 7 (0.7%) of the 983. Only cholecystectomy is necessary to be performed for Tis or T1 cancer, and surgery has to be changed to radical surgery for T2 cancer or deeper invasion. Laparoscopic cholecystectomy is already an established standard operation. In the presence of acute or severe chronic inflammation, special attention should be paid to these points.

Significance of CD44s and CD44v6 expression in pancreaticobiliary maljunction.

BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) is a high risk factor in biliary tract cancer. The relation of CD44s and CD44v6 expression in biliary epithelium with PBM and the carcinogenetic process was immunohistochemically examined. METHODOLOGY: One hundred and seven lesions were randomly selected from gallbladders and bile ducts, which were resected from 25 patients with PBM, and immunostaining for CD44s, CD44v6 and MIB-1 was carried out. RESULTS: Among gallbladder lesions, cancerous lesions (dysplasia, cancer) had a higher immunoreactivity with statistical significance for CD44s and CD44v6 compared to non-cancerous lesions (normal, hyperplasia). In bile ducts as well, cancerous lesions had a higher immunoreactivity for CD44s and CD44v6. In both gallbladders and bile ducts, positive cases of CD44s and CD44v6 had a higher statistical significance of Ki-67 labeling index in comparison with negative cases. CONCLUSIONS: In biliary epithelium with PBM, CD44 was indicated to be strongly related to cancer progression via an increase of cellular proliferative potential.