Hirokazu Kiyozaki

Segmental Small Bowel Transplantation in the Rat: Comparison of Lipid Absorption Between Jejunal and Ileal Grafts

BACKGROUND From the immunological point of view, it is very important to evaluate the efficacy of segmental small bowel transplantation and to determine which part of the intestine, jejunum, or ileum should be used. In the present study, we investigated the absorptive function of the transplanted jejunum and ileum in the rat. METHODS Syngeneic segmental small bowel transplantation (jejunal or ileal grafting) was performed. After surgery, body weight and fecal fat excretions were measured. In addition, bile acid concentration in bile juice was measured, and the response of both serum lipase and bile flow rate after oleic acid stimulation was evaluated. Recanalization of the lymphatic vessels was investigated by lymphangiography. RESULTS There was no significant difference in body weight change between normal controls, jejunum-transplanted rats, and ileum-transplanted rats. In short gut rats, however, body weight was significantly impaired. Fecal fat excretion in short gut rats was the highest in the four groups, and it was significantly lower in ileal grafts than in jejunal grafts. Ileum-transplanted rats also showed a significantly higher bile acid concentration in bile juice than jejunum-transplanted rats. After oleic acid stimulation, serum lipase responded better in ileal transplants than in jejunal transplants, but the bile flow rate did not show significant change in either group. Recanalization of the lymphatic vessels was established on the 28th postoperative day. CONCLUSIONS These results clearly show that ileal transplantation is more conducive to lipid absorption than jejunal transplantation.

Sclerosing Encapsulating Peritonitis (SEP) as a Delayed Complication of Continuous Hyperthermic Peritoneal Perfusion (CHPP) : Report of a Case

Abstract.A 47-year-old woman underwent curative resection of advanced gastric cancer, followed by continuous hyperthermic peritoneal perfusion (CHPP). She was readmitted to our hospital 6 months after the operation with a diagnosis of postoperative adhesional ileus. An exploratory laparotomy revealed that the small intestine, which had normal serosa, was folded and enveloped in thickened peritoneum like a “cocoon,” suggesting sclerosing encapsulating peritonitis (SEP). Because of tight adhesion in the ileocecal region, resection of the membrane was performed only in the feasible areas, followed by side-to-side anastomosis between the ileum and ascending colon. The patient has remained well for 15 months since this operation with no radiological signs or laboratory findings of recurrence. When small bowel obstruction does not show improvement with conservative treatment, and if the possibility of peritoneal cancer recurrence is excluded by thorough examinations, it is important to perform laparotomy early to resolve the symptoms of bowel obstruction and restore the patients quality of life.

The accumulation of DNA demethylation in Sat α in normal gastric tissues with Helicobacter pylori infection renders susceptibility to gastric cancer in some individuals

Helicobacter pylori (HP) infection is widely recognized as a risk factor for gastric cancer, but only a minority of infected individuals develop gastric cancer. The aim of this study was to determine whether DNA demethylation in non-cancerous gastric mucosa (NGM) significantly enhances susceptibility to gastric cancer. A total of 165 healthy volunteers, including 83 HP-positive and 82-negative individuals, as well as 83 patients with single and 18 with synchronous double gastric cancer (GC) were enrolled in this study. The relative demethylation levels (RDLs) of repetitive sequences, including Alu, LINE-1 and Sat α, were quantified by real-time methylation-specific polymerase chain reaction. The Alu RDL did not exhibit any differences within each respective group, whereas LINE-1 RDL was significantly elevated in cancer tissues compared with the NGM in the other groups (P<0.001). Our results indicated that a gradual increase in Sat α RDL correlated with HP infection and cancer development. Sat α RDL was significantly elevated in the NGM in HP-positive compared with HP-negative (P<0.001), and significantly elevated in cancer tissues (P<0.001). Although the Sat α RDL of the NGM in the total population increased in an age-dependent manner, it was significantly increased in a fraction of younger GC patients (<45 years) compared with all of the others (45 years or older, P=0.0391). In addition, double GC exhibited a significantly higher Sat α RDL in the NGM compared with single GC (P=0.0014). In these two fractions, Sat α RDL in the NGM exhibited an inverse correlation with age. In conclusion, the present study demonstrated that the accumulation of DNA demethylation in Sat α RDL in the NGM with HP infection potentially renders susceptibility to gastric cancer in a fraction of GC patients younger than 45 years or in patients with multiple cancers.

Lidocaine metabolite formation as a measure of perioperative liver function

In order to determine whether lidocaine metabolism, as the formation of monoethylglycinexylidide (MEGX), could be used as a quantitative index of perioperative liver function, serum levels of MEGX in 31 surgical patients were measured and compared with the results of conventional liver function tests. A significant correlation was found between the values of MEGX and ICGR15 in 20 of the 31 patients. The values of ICGR15 were lower than 20% in patients whose MEGX values were above 60 ng/ml and 20% or higher in those with MEGX values of lower than 60 ng/ml. There was also a significant correlation between MEGX values and antithrombin III values, and between MEGX values and the postoperative maximum levels of aspartate aminotransferase. However, no correlation was found between MEGX values and other preoperative conventional liver function tests in any of the 31 patients. We suggest that a cut-off MEGX value of 60 ng/ml be used as an indicator for satisfactory preoperative liver function. MEGX formation could be a useful prognostic index for patients who have undergone surgical procedures for liver disease, and employed as a quantitative assessment of perioperative liver function.

Giant fibrovascular polyp of the esophagus successfully treated by endoscope-assisted resection

Fibrovascular polyps of the esophagus are extremely rare. A 52-year-old woman had the sensation of food sticking in her throat for 3 weeks. Examination revealed a polypoid lesion within the esophagus that extended from the pyriform sinus to the distal esophagus above the gastric cardia. With the patient under general anesthesia, the stalk of the lesion was cut through the rigid laryngoscope; however, the tumor could not be retrieved through the mouth. Large biopsies of the lesion were taken. The remaining lesion was later passed in the fecal matter. Pathological findings were consistent with the features of fibrovascular polyps.

Cecal perforation with an ascending colon cancer caused by upper gastrointestinal endoscopy

Colonic perforation caused by upper gastrointestinal (GI) endoscopy is extremely rare. A 69-year-old woman was referred to our hospital because of abdominal fullness. Colonoscopy could be performed only up to the hepatic flexure due to an elongated colon and residual stools. Because her symptoms improved, upper GI endoscopy was performed 11 days later. The patient developed severe abdominal pain two hours after the examination. Abdominal X-ray and computed tomography showed massive free air. Immediate laparotomy was performed for the intestinal perforation. After removal of stool, a perforation site was detected in the cecum with an invasive ascending colon cancer. Therefore, a right hemicolectomy, ileostomy, and transverse colostomy were performed. Although she developed postoperative septicemia, the patient was discharged 38 days after admission. Seven months postoperatively, the patient died of lung, liver, and brain metastases. Even in cases with a lesion that is not completely obstructed, it is important to note that air insufflations during upper GI endoscopy can perforate the intestinal wall in patients with advanced colon cancer.

Nonrecurrent inferior laryngeal nerve in patients with esophageal cancer: report of two cases

The preservation of the recurrent laryngeal nerve is a fundamental skill in cervical procedure such as thyroid, parathyroid or esophagus surgery. Any damage to this nerve could lead to permanent ipsilateral vocal cord paralysis. Therefore this iatrogenic complication must be absolutely avoided by surgeons. However, surgeons rarely encounter the nonrecurrent inferior laryngeal nerve. The aim of this report is to describe this nerve anomaly and its causes based on our recent experience obtained during two esophageal operations.

Morphological response contributes to patient selection for rescue liver resection in chemotherapy patients with initially un-resectable colorectal liver metastasis

Morphological response is considered an improved surrogate to the Response Evaluation Criteria in Solid Tumors (RECIST) model with regard to predicting the prognosis for patients with colorectal liver metastases. However, its use as a decision-making tool for surgical intervention has not been examined. The present study assessed the morphological response in 50 patients who underwent chemotherapy with or without bevacizumab for initially un-resectable colorectal liver metastases. Changes in tumor morphology between heterogeneous with uncertain borders and homogeneous with clear borders were defined as an optimal response (OR). Patients were also assessed as having an incomplete response (IR), and an absence of marked changes was assessed as no response (NR). No significant difference was observed in progression-free survival (PFS) between complete response/partial response (CR/PR) and stable disease/progressive disease (SD/PD), according to RECIST. By contrast, PFS for OR/IR patients was significantly improved compared with that for NR patients (13.2 vs. 8.7 months; P=0.0426). Exclusion of PD enhanced the difference in PFS between OR/IR and NR patients (15.1 vs. 9.3 months; P<0.0001), whereas no difference was observed between CR/PR and SD. The rate of OR and IR in patients treated with bevacizumab was 47.4% (9/19), but only 19.4% (6/31) for patients that were not administered bevacizumab. Comparison of the survival curves between OR/IR and NR patients revealed similar survival rates at 6 months after chemotherapy, but the groups exhibited different survival rates subsequent to this period of time. Patients showing OR/IR within 6 months appeared to be oncologically stable and could be considered as candidates for surgical intervention, including rescue liver resection. Comparing the pathological and morphological features of the tumor with representative optimal response, living tumor cells were revealed to be distributed within the area of vascular reconstruction induced by bevacizumab, resulting in a predictive value for prognosis in the patients treated with bevacizumab. The present findings provided the evidence for physicians to consider patients with previously un-resectable metastatic colorectal cancer as candidates for surgical treatment. Morphological response is a useful decision-making tool for evaluating these patients for rescue liver resection following chemotherapy.

Significance of the Difference in the Size of Liver Tumors in the Managementof Patients with Colorectal Liver Metastases

Background: The combination of chemotherapy and surgery is currently accepted for the treatment of patients with technically resectable colorectal liver metastases. It is, however, hard to determine which of these modalities should be the forward treatment. In this study, we assessed the usefulness of the difference in tumor size assessed in pretherapeutic imaging in the selection of chemotherapy in these patients. Methods: We present a retrospective review of 80 consecutive colorectal liver metastases without extrahepatic tumors. The relapse-free survival (RFS), progression-free survival (PFS) and overall survival (OS) were evaluated and compared between patients who underwent surgery (n=66) and chemotherapy (n=14) according to clinical features. In particular, we addressed pretherapeutic imaging studies including the distribution and number of metastatic liver tumors. In addition, the ratio of tumor size (largest to smallest tumor) was calculated; two groups classified as R<5 (ratio <5) and R ≥ 5 (ratio ≥ 5) were compared. Results: Univariate analysis was performed in the surgery group; significant differences in RFS were found regarding time of occurrence, the number of tumors and the ratio of tumor diameters. Multivariate analysis showed that the ratio of tumor size, R ≥ 5, was the only independent prognostic risk factor concerning both RFS and OS. We then compared the outcome of patients with prognostic risk factors between surgery and chemotherapy. Surgery achieved significantly better OS than chemotherapy, with the exception of the R ≥ 5 group. No difference in OS, in addition to RFS and PFS, was seen in the R ≥ 5 groups regardless of treatment. Conclusion: CRC patients with resectable liver metastases with R ≥ 5 showed no significant difference in outcome using surgery or chemotherapy. Chemotherapy could be used as an alternative to forward surgery to address oncological concerns such as the presence of latent metastases or poor treatment outcome in these patients.

Lymphatic invasion in small differentiated-type mucosal gastric cancer

Endoscopic resection for early gastric cancer is indicated for patients who are at negligible risk of lymph node metastasis. A 71-year-old female underwent endoscopic resection for a 15-mm differentiated-type mucosal gastric tumor, as recommended in the Japanese treatment guidelines. A histological examination revealed lymphatic invasion. Therefore, we performed laparoscopy-assisted distal gastrectomy and D1+ lymph node dissection. A histological examination detected no.3 lymph node metastasis, but no residual cancer cells were observed at the site of the endoscopic resection. This case is rare as lymphatic invasion and lymph node metastasis are highly unusual in small differentiated-type mucosal gastric cancer. Having experienced this case, we consider that en-bloc endoscopic resection of such lesions is extremely important, as it allows precise histological examinations to be performed, which can determine the necessity of additional treatment.