Laparoscopic-assisted robotic distal gastrectomy for gastric cancer by Billroth II reconstruction.

BACKGROUND: There are several reconstructions in distal gastrectomy for gastric cancer, and there is no clear definition regarding the method selection. The optimal reconstruction is likely to vary according to the surgical setting, and the optimal reconstruction for robotic distal gastrectomy is urgently needed. In addition, as robotic gastrectomy is getting popular, cost and operative time are pressing issues of robotic gastrectomy. METHODS: Gastrojejunostomy was planned with Billroth II reconstruction using a linear stapler arranged specifically for a robotic approach. After firing the stapler, the common insertion orifice of the stapler was closed using a 30 cm long non-absorbable barbed suture, and continuously, the afferent loop of the jejunum was lifted to the stomach with the same barbed suture. In addition, we introduced laparoscopic-assisted robotic gastrectomy, using extracorporeally inserted laparoscopic devices from the assistant port. Scissors, clips, and linear staplers were all laparoscopic tools inserted extracorporeally. RESULTS: Twenty-one gastric cancer patients underwent laparoscopic-assisted robotic distal gastrectomy by Billroth II reconstruction with our modifications. There were no anastomosis-related complications such as leakage, stenosis, or bleeding. There were 2 cases of aspiration pneumonia (Clavien-Dindo grade 2), 1 case of pancreatic juice leakage (grade 3a), and 1 case of delayed gastric emptying (grade 1). CONCLUSION: We successfully arranged Billroth II reconstruction for robotic distal gastrectomy with fewer operative and postoperative complications. Laparoscopic-assisted robotic gastrectomy using extracorporeally inserted devices, and continuous suturing using a barbed suture will reduce the time and cost of robotic gastrectomy.

A novel method of anvil placement of circular stapler for esophagojejunostomy in laparoscopic total gastrectomy for gastric cancer: results of consecutive 200 cases.

BACKGROUND: Laparoscopic total gastrectomy for gastric cancer is still a demanding operation because of technical difficulties, especially of intracorporeal esophago-jejunal anastomosis. METHODS: We introduced a newly designed method of anvil placement of circular stapling devices (CS) for laparoscopic esophagojejunostomy (EJS). A small incision was made on the anterior wall of the stomach, from which the anvil was inserted into the stomach and proceeded to the thoracic esophagus. Then, the abdominal esophagus was transected by a linear stapler, and the anvil into the esophagus was drawn back to the esophageal stump by pulling out the cotton tape pre-attached to the anvil. Intracorporeal EJS by Roux-en-Y reconstruction was performed by CS inserted into the abdominal cavity from the umbilical wound. RESULTS: A total of consecutive 200 gastric cancer patients underwent laparoscopic total gastrectomy using this method. There was no operative mortality. Anastomotic complications occurred in 12 cases (6.0%): 9 cases of stenosis (4.5%) and 3 cases of bleedings (1.5%). Anastomotic leakage was not observed. As for non-anastomotic complications, there occurred 2 pulmonary complications (1.0%), 3 pancreatic leakages (1.5%), and 8 bowel obstructions due to internal hernia (4.0%). With a median follow-up period of 47.1 months, 5-year overall survival for assessable patients (n = 193) was 60.3% (95% CI 52.6-67.2). The total rate of peritoneal recurrence was 9.8%. CONCLUSION: Our new method of anvil placement for laparoscopic EJS with CS is safe and feasible with favorable survival outcomes. It eliminates the need for suturing, and will promote the clinical application of laparoscopic total gastrectomy for gastric cancer. CLINICAL TRIALS: UMIN000046119.

Re-do laparoscopic esophagojejunostomy for anastomotic stenosis after laparoscopic total gastrectomy in gastric cancer.

PURPOSE: Anastomotic stenosis of esophagojejunostomy after total gastrectomy has a substantial impact on the postoperative quality of life of the patient. If conservative treatment doesn't work, surgical intervention should be considered. However, redoing esophagojejunostomy is an extremely demanding procedure. Especially in the case where the primary surgery was performed laparoscopically, it is an unmet problem to maintain minimal invasiveness in re-do surgery. METHODS: We report 3 cases of re-do esophagojejunostomy laparoscopically performed for anastomotic stenosis after laparoscopic total gastrectomy in gastric cancer, in whom endoscopic balloon dilation did not work. RESULTS: Each patient underwent a re-do esophagojejunostomy laparoscopically. The mean operation time was 293 min, and the mean blood loss was 56 ml. There was no anastomosis-related complication, and they were discharged from hospital on 11-16 postoperative days. At the time of discharge, oral food intake was 100% in each patient. One year after the operation, follow-up endoscopic exams showed no anastomotic stenosis. CONCLUSION: Re-do laparoscopic esophagojejunostomy for anastomotic stenosis after laparoscopic total gastrectomy was safely and successfully performed. It brings patients minimal invasiveness continuously from the initial surgery. Re-do laparoscopic esophagojejunostomy could be one of the options for anastomotic stenosis resistant to conservative treatment.

Intrahepatic bile duct rupture associated with IgG4-related sclerosing cholangitis presenting hepatic inflammatory pseudotumor.

A 67-year-old man with a low-grade fever was found to have a 25-mm diameter tumor of the left hepatic umbilical portion. The tumor was accompanied by occlusion of the left portal vein. Positron emission tomography using fluorodeoxyglucose showed that the tumor had abnormally high metabolic activity. Magnetic resonance imaging revealed the left hepatic duct segmental narrowing. There was a mild elevation in serum IgG4 (206 mg/dL). Intrahepatic cholangiocarcinoma was suspected. Instead of planned hepatectomy, the patient was forced to undergo emergency surgery for biliary panperitonitis caused by intrahepatic bile duct rupture. Intraoperative ultrasonography revealed a hypoechoic tumor-like thickened Glissonean sheath and needle biopsy was performed. Histologic examination confirmed fibrous tissue with IgG4-positive plasma cell infiltration without neoplastic proliferation. He was diagnosed with IgG4-related sclerosing cholangitis (IgG4-SC) presenting hepatic inflammatory pseudotumor. After his general condition improved, he underwent left hepatectomy. Macroscopic findings showed extreme fibrosis of the Glissonean sheath of the umbilical portion, and diffuse granular lesion aggregated in the left lateral segment. Microscopic examination confirmed chronic cholangitis and dense portal fibrosis in the umbilical portion and diffuse xanthogranulomatous inflammation. This is the first case report of spontaneous rupture of the intrahepatic bile duct in patient with IgG4-SC.

[Successful Administration of Alternate-Day, Low-Dose S-1 in a Patient with Recurrent Esophageal Cancer with a Poor Compliance Profile].

A 79-year-old woman had recurrence in the mediastinal lymph node 6 months after curative resection of advanced esophageal cancer(pStage Ⅲ). After radiation therapy and 12 courses of chemotherapy with docetaxel, new recurrent tumors progressed in the mediastinum and apical region of the left lung, and her performance status(PS)deteriorated to grade 3. Alternate-day, low-dose S-1 chemotherapy was started at a dose of 60mg/day. Tumors decreased in size within 6 months, and her PS improved from grade 3 to 0. She had been treated for 33 months without severe adverse events until disease progression. So far, we have experienced in clinical practices that the alternate-day S-1 administration was tolerable for patients who were unfit for the standard daily administration. Alternate-day, low-dose S-1 administration may be a sustainable and effective option in S-1 chemotherapy in patients with recurrent esophageal cancer with impaired PS.

[A Case of Type 1A Charcot-Marie-Tooth Disease Manifested by Oxaliplatin Administration of Neoadjuvant Chemotherapy in a Gastric Cancer Patient].

Herein, we report the manifestation of type 1A Charcot-Marie-Tooth disease(CMT)in a 54-year-old female gastric cancer patient caused by oxaliplatin(L-OHP)of neoadjuvant chemotherapy containing S-1 plus L-OHP(G-SOX). In this case, peripheral sensory neuropathy(PSN)appeared in both upper limbs immediately after the administration of L-OHP. Subsequently, we observed sensory neuropathy of gloves-socks type in both the upper and lower limbs and motor neuropathy in both lower limbs, which caused the patient to be unable to sit up. Physical examination revealed upside-down champagnebottle- like mild atrophy in both lower limbs and hollow feet in both legs, as well as the disappearance of deep tendon reflexes in both lower limbs. In her family history, her eldest daughter had undergone Achilles tendon elongation surgery for suspected CMT at the age of 3 years. Considering these, she was suspected to have CMT and was finally diagnosed with type 1A CMT based on genetic testing. In anti-cancer treatments that cause PSN(not just by L-OHP), possible involvement of occult peripheral nerve disease like CMT should be considered when more rapid and untypical PSN appears after the administration of anti-cancer drugs.

[Rupture of Ovarian Metastasis from Cecal Cancer during Chemotherapy - A Case Report Suggestive of Bilateral Salpingo-Oophorectomy].

A 66-year-old woman was diagnosed with advanced cecal cancer with metastases to her right ovary, peritoneum, and liver. Ileocecal resection and right salpingo-oophorectomy were performed as cytoreduction surgery before systemic chemotherapy. The colon cancer metastasized to her left ovary during chemotherapy and grew rapidly until it ruptured spontaneously, although the other metastases sites continued to respond to treatment. Emergent left salpingo-oophorectomy was performed. Pathological findings confirmed ovarian metastasis from colon cancer. Ovarian metastases are less responsive to systemic chemotherapy compared to extra-ovarian metastasis and the rapid growth sometimes occurs as a related symptom. Bilateral salpingo-oophorectomy might be recommended in cytoreduction surgery even if the ovarian metastasis is unilateral.

Polymorphisms in the Helicobacter pylori NY43 strain and its prophage-cured derivatives.

This study aimed to determine the characteristics of the Helicobacter pylori host NY43 strain and its prophage-cured derivative. H. pylori colonizing the human stomach cause many diseases. They show high genetic diversity, allowing the development of mutant strains that can form bacterial communities adapted to specific environmental conditions. Bacteriophage activities are associated with bacterial evolution, including pathogenicity development. Herein, we reported the complete genome sequence and genomic organization of two H. pylori prophages, KHP30 and KHP40; the effects of KHP30 on the behaviours of NY43 are not yet known. We showed that approximately 57 % prophage-cured derivatives spontaneously appeared in the exponential phase during liquid culture, and the biological characteristics of these derivatives differed from those of the host NY43. KHP30 reinfected the cured derivatives, and the curing ratio was influenced by culture conditions. KHP30 was shown to promote the development of a flexible H. pylori community with variable characteristics.

Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report.

BACKGROUND: Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% of the pretreated patients with metastatic colorectal cancer in the pivotal studies, radiological response has rarely been reported. Severe adverse events associated with regorafenib are known to occur during the first and second courses of treatment. We present a case of a 62-year-old Japanese patient whose metastatic colorectal cancer has been responding to treatment with regorafenib for 2 years. CASE PRESENTATION: A 54-year-old Japanese man visited our institute exhibiting general malaise, and he was diagnosed with ascending colon cancer in April 2006. He underwent right hemicolectomy, and the final staging was T3N0M0, stage II. After 19 months, pulmonary metastasis and anastomotic recurrences were detected, and a series of operations were performed to resect both metastatic lesions. After that, liver metastasis, a duodenal metastasis with right renal invasion, right adrenal metastasis, and para-aortic lymph node metastases were observed during follow-up, and chemotherapy and resection were performed. The patient had metastatic para-aortic lymph nodes after the fifth tumor resection and underwent multiple lines of chemotherapy in April 2014. Regorafenib monotherapy was started at 80 mg/day. Then, regorafenib was increased to 120 mg/day in the second cycle. Regorafenib monotherapy led to 60% tumor shrinkage within the initial 2 months, and the tumor further decreased in size over 4 months until it became unrecognizable on imaging studies. The clinical effects of regorafenib monotherapy have shown a partial response according to Response Evaluation Criteria in Solid Tumors criteria. No severe adverse events were observed, except for mild fatigue and hand-foot syndrome. The patient has received 24 courses of regorafenib over 2 years without exhibiting tumor progression. CONCLUSIONS: To the best of our knowledge, this is the longest treatment with regorafenib without tumor progression ever reported. A reduced dosage of regorafenib at induction may ameliorate the cutaneous and hepatic toxicity associated with its use.

[Successful Administration of Regorafenib to a Metastatic Colon Cancer Patient with Impaired Performance Status by Reducing the Initial Dose].

A 59-year-old woman had recurrences in the spleen and lung 10 years after radical excision of cecal cancer. After 27 months of treatment with 5-fluorouracil/Leucovorin, oxaliplatin, irinotecan, bevacizumab, and anti-EGFR antibodies, multiple bone metastases and a left adrenal metastasis developed, and the patient's performance status (PS) deteriorated to grade 3. Regorafenib was administered at 80 mg/day. The pain and appetite improved within 2 courses, and her PS improved from grade 3 to 2. Regorafenib was increased to 120 mg/day for the 2nd course, and the patient was treated for 5 months without severe adverse effects. Regorafenib is considered to be a salvage-line treatment only for patients in relatively good condition, because full-dose regorafenib treatment often leads to severe adverse effects. Dose escalation of regorafenib from the low initial dose of 80 mg/day may be a safe and effective way of providing an opportunity of this chemotherapy to patients with impaired PS.

[Long-term progression-free survival after reduction surgery and postoperative low-dose imatinib administration for multiple liver metastases of duodenal gastrointestinal stromal tumor].

A fifty-six year-old woman visited our institute, suffering from lower abdominal pain. A tumor was palpable in the pelvic cavity, having the diameter of 9.7 cm, as measured by transvaginal ultrasonography (US). Computed tomography and magnetic resonance imaging (MRI) revealed a high contrast-enhancement and the central necrosis of the tumor. Surgical resection was performed, and the tumor was found to have originated in the duodenum. Immunohistochemistry confirmed positive KIT, and the mitotic index was 4 per 50 high power field, so that the final diagnosis was a gastrointestinal stromal tumor of intermediate risk. After two years of observation, multiple liver metastases were found. Hepatectomy was performed as a volume reduction surgery, leaving three small lesions in the remnant liver. Imatinib administration was initiated at 400 mg a day two weeks after the surgery, but was interrupted two weeks later because of severe anorexia and a body weight gain of 7 kg due to the increased ascites and edema. Imatinib was resumed at 200 mg/day after a one-month interval. She has been enjoying relapse-free survival for 8 years since the recurrence was diagnosed. Although neither reduction surgery nor dose reduction of imatinib below 300 mg/day is recommended, there may be a possibility that a smaller tumor might be controlled by a lower dose of imatinib.

[A case of pagetoid carcinoma of the breast in nearly complete response by primary systemic therapy].

A 62-year-old female presented with an erosion of the left nipple. At the preoperative examination, it was diagnosed as a Pagetoid carcinoma with an invasive carcinoma. After primary systemic therapy(weekly paclitaxel/trastuzumab), we performed an operation. The only remaining Paget cell was confirmed in the resected specimen, and no other malignant cells were confirmed. There is no report that the preoperative chemotherapy for the Pagetoid carcinoma with an invasive carcinoma. The patient has had no evidence of recurrence 1. 5 years after the operation.

[Recurrent liver sigmoid cancer responding remarkably to neoadjuvant chemotherapy using bevacizumab/XELOX: report of a case].

A 65-year-old male experiencing the recurrence of a solitary sigmoid cancer liver tumor was treated with bevacizumab (Bev)/XELOX chemotherapy, because he had refused surgical resection. After 5 courses, CT findings showed a partial response( 80% size-reduction)of the recurrent liver tumor. There was no recurrence in any other organ. He then requested hepatectomy, so we performed it, and there were no complications. The histological diagnosis was metastatic liver tumor, the estimation of the histological change by chemotherapy was Grade 2, and no abnormalities were found in the background of the liver. Bev/XELOX was relatively safe and successful for pre-operative patients with liver tumor recurrence.

A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers.

Previously, we clarified the surface antigen profiles of hepatic progenitor cells (HPCs) in fetal liver tissue as the CD49f(+)CD45(-)Thy1(-) cell fraction. However, these cells were a heterogeneous cell population containing various stages of differentiation. This study aimed to detect more immature HPCs, using a novel surface antigen, gp38. After the collagenase digestion of fetal livers harvested from E13.5 to E18.5 fetal mice, HPCs were obtained and divided into two subpopulations using flow cytometry: gp38-positive HPCs, and gp38-negative HPCs. Both types of HPCs were characterized by immunocytochemistry and RT-PCR. The proliferative activity was compared by BrdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay. Furthermore, the comprehensive gene expression was investigated by DNA microarray. Both types of HPCs expressed alpha-fetoprotein. However, the gp38-positive HPCs derived from E13.5 fetal livers did not express albumin or cytokeratin 19, while the gp38-negative HPCs did. DNA microarray revealed that some genes related to the Wnt signal pathway were up-regulated in the gp38-positive HPCs. Furthermore, Wnt3a had a proliferative effect on the gp38-positive HPCs. In conclusion, the gp38-positive HPCs derived from fetal liver tissue until E13.5 could therefore be candidates for hepatic stem cells in the fetal liver.

Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model.

BACKGROUND: The use of cell transplantation as an alternative therapy for orthotopic liver transplantation has been widely anticipated due to a chronic donor shortage. We previously reported the method used to enrich hepatic progenitor cells (HPCs) forming cell aggregations. In this study, we transplanted HPCs into the liver injury model mice to determine whether HPC transplantation may improve the liver dysfunction. METHODS: We obtained donor cells from E13.5 fetal livers of green fluorescent protein (GFP) transgenic mice. We transplanted GFP-positive fetal liver cells into the transgenic mice which express diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Subsequently, we induced selective liver injury to recipient mice by DT administration. We then evaluated the engraftment of the transplanted cells and their effect on survivorship. RESULTS: The low dose of DT induced sublethal liver injury and the high dose of DT was lethal to the liver injury model mice. The transplanted GFP-positive cells were engrafted into the recipient livers and expressed albumin, resembling mature hepatocytes. They continued to proliferate, forming clusters. The survival rate at 25 days after transplantation of the cell-transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in comparison to that of the sham-operated group (0 of 20; 0%). CONCLUSIONS: The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice. We therefore propose that HPCs are a desirable cell source for cell transplantation.

Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage.

ESCs are a potential cell source for cell therapy. However, there is no evidence that cell transplantation using ESC-derived hepatocytes is therapeutically effective. The main objective of this study was to assess the therapeutic efficacy of the transplantation of ESC-derived endodermal cells into a liver injury model. The beta-galactosidase-labeled mouse ESCs were differentiated into alpha-fetoprotein (AFP)-producing endodermal cells. AFP-producing cells or ESCs were transplanted into transgenic mice that expressed diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Selective damage was induced in the recipient hepatocytes by the administration of DT. Although the transplanted AFP-producing cells had repopulated only 3.4% of the total liver mass 7 days after cell transplantation, they replaced 32.8% of the liver by day 35. However, these engrafted cells decreased (18.3% at day 40 and 7.9% at day 50) after the cessation of DT administration, and few donor cells were observed by days 60-90. The survival rate of the AFP-producing cell-transplanted group (66.7%) was significantly higher in comparison with that of the sham-operated group (17.6%). No tumors were detected by day 50 in the AFP-producing cell-transplanted group; however, splenic teratomas did form 60 days or more after transplantation. ESC transplantation had no effect on survival rates; furthermore, there was a high frequency of tumors in the ESC-transplanted group 35 days after transplantation. In conclusion, this study demonstrates, for the first time, that ESC-derived endodermal cells improve the survival rates after transplantation into mice with induced hepatocellular injury. Disclosure of potential conflicts of interest is found at the end of this article.

Prognostic factors and scoring system for survival in colonic perforation.

BACKGROUND/AIMS: No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. METHODOLOGY: Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. RESULTS: The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. CONCLUSIONS: Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.