Xanthogranulomatous cholecystitis: a review of 31 patients.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory gallbladder disease which is difficult to diagnose and treat; XGC may be confused with gallbladder cancer. The present study aimed to evaluate the clinical and radiological features and surgical outcomes, with the aim to determine the appropriate treatment approaches for XGC. METHODS: This retrospective study analyzed the clinical characteristics, intraoperative findings, and postoperative outcomes of 31 patients (2.0%) who were diagnosed with XGC based on histopathological findings among 1513 patients who underwent cholecystectomy at our hospital between January 2010 and July 2019. RESULTS: Preoperative ultrasonography and computed tomography findings indicated acute cholecystitis, chronic cholecystitis, and suspicious XGC in 26 (83.9%) patients with thickening of the gallbladder wall and suspicious gallbladder cancer in 5 (16.1%) patients. Abdominal pain and jaundice were observed in 18 (58.1%) patients and 5 (16.1%) patients, respectively. Biliary drainage before surgery was performed in 21 (67.7%) patients. Laparoscopic cholecystectomy, which was performed in 23 (74.2%) patients, was converted to open cholecystectomy in 12 (52.2%) of these 23 patients. Among the patients with other diseases treated during the study period, laparoscopic cholecystectomy was performed in 1377 patients and converted to open surgery in 71 (5.2%) patients. Five patients with suspicious gallbladder cancer underwent open surgery. In these patients, intraoperative frozen section analysis was useful in distinguishing between XGC and gallbladder cancer and was important in avoiding unnecessarily extended surgery. CONCLUSION: Laparoscopic cholecystectomy for XGC is possible, but often difficult due to severe inflammation. The frequency of conversion to open surgery is higher in patients with XGC than those with other forms of cholecystitis. XGC may resemble gallbladder cancer based on the diagnostic imaging findings, and intraoperative frozen section analysis is essential to avoid unnecessarily extended surgery.

Additional surgery after endoscopic submucosal dissection for colorectal cancer: a review of 53 cases.

BACKGROUND: Endoscopic submucosal dissection (ESD) allows the en bloc resection of tumors and is particularly indicated for T1 colorectal cancer. The number of patients undergoing additional surgery after colorectal ESD is increasing. This study aimed to retrospectively evaluate the efficacy and long-term outcomes in patients with additional surgery. METHODS: Of 1018 patients who underwent colorectal ESD in our hospital between February 2010 and July 2018, 53 patients who underwent additional surgery in our hospital were retrospectively analyzed and investigated for their clinicopathological characteristics. The need for additional surgery was determined by a pathological examination according to the guideline [1]. RESULTS: In total, 53 patients (24 men, 29 women; mean age, 68.2 years; mean tumor diameter, 30.5 mm) were included. Laparoscopic surgery was performed in 47 (88.7%) patients. Liver metastases were preoperatively observed in one patient, for whom hepatectomy was simultaneously performed. All procedures included pathological R0 resection. Postoperative complications occurred in 9 (17.0%) patients. There were no complications requiring reoperation. Fifteen (28.3%) patients had a positive vertical margin; of these patients, residual tumor was observed in the resected specimens of two (13.3%) patients. Eight patients (15.1%) had lymph node metastasis (LNM): four (25.0%) and four (10.8%) of 16 and 37 patients with and without vascular invasion, respectively. Eleven patients (20.8%) had grade 2 or 3 tumor budding, and four (36.4%) of these had LNM. Postoperative recurrence was observed in two (3.8%) patients. CONCLUSION: Additional surgery after ESD for T1 colorectal cancer was effective and had good long-term outcomes.

[A Case of Gastrointestinal Stromal Tumor in the Rectum with Preservation of Anal Function after Neoadjuvant Chemotherapy UsingImatinib].

A n 81-year-old woman was admitted to our institution. Computed tomography performed before transcatheter aortic valve implantation(TAVI)for aortic stenosis revealed a tumor in the rectum. Lower endoscopy revealed that the tumor was a 60mm submucosal tumor and located 2 cm from the anal verge. Abiopsy revealed the diagnosis to be gastrointestinal stromal tumor(GIST). Although the tumor was located near the anal verge and might have invaded the surrounding organs, neoadjuvant chemotherapy(NAC) with 400mg/day of imatinib was initiated to preserve anal function as requested by the patient and her family. After 3 months, the tumor size decreased by 36.6% and there was a decrease in rate of tumor shrinkage. We performed transanal tumor resection and temporary colostomy. After 6 months, we performed colostomy closure, and the patient has remained recurrence-free and is continuing chemotherapy.

[A Case of Advanced Gastric Cancer with Liver Metastases Treated with Curative Conversion Therapy after S-1 plus Oxaliplatin].

An 81-year-old man was referred to our hospital. Upper gastrointestinal endoscopy revealed a type 2 tumor in the antrum of the stomach. The histopathological findings showed a moderately differentiated HER2-negative adenocarcinoma. Two low-density areas of 17mm and 26mm in diameter were observed in the liver S6 and S8respectively at the CT scan. Nine courses of S-1 plus oxaliplatin(SOX)therapy were administered to this patient with gastric cancer and liver metastases. Since both the primary tumor and the liver metastases were significantly reduced by the chemotherapy, distal gastrectomy(D2 dissection)and partial liver resection(liver S6, S8)were performed. The histopathological findings revealed no tumor cells in the primary tumor, lymph nodes, and liver metastases, with a histologic effect of Grade 3. The patient underwent adjuvant therapy with S-1. He has been alive without recurrence for 11 months post-surgery.

[Two Cases of Advanced Gastric Cancer with Simultaneous Liver Metastasis with Long-Term Recurrence-Free Survival].

We report 2 cases of postoperative long-term survival of gastric cancer with synchronous liver metastasis. Case 1 was a 65- year-old man. Examination for anemia revealed advanced type 5 cancer in the antrum and suspected invasion of the transverse colon. A nodule 15mm in diameter suspected to be metastasis was also found in the liver S2. As no unresectable factors were present, partial hepatectomy, partial transverse colon resection, and distal gastrectomy were performed. Postoperatively, S-1 chemotherapy was administered for 14 months. Seven years after surgery, the patient is alive without recurrence. Case 2 was a 67-year-old woman. Examination for anemia revealed advanced type 2 cancer in the lower gastric body and a nodule 12mm in diameter suspected to be liver metastasis in the liver S8. Partial resection of the liver, total gastrectomy, cholecystectomy, and splenectomy were performed because no unresectable factors were observed. Postoperatively, chemotherapy with S-1 was administered for 38 months. Six years after surgery, she is alive without recurrence. Although there is no clear evidence for radical surgery for gastric cancer with simultaneous liver metastases, these results indicate that resection may be considered in cases with small numbers of metastases.

[Efforts toward qualitative and quantitative improvements of cancer clinical trials at regional designated cancer care hospitals-through full support for cancer clinical trials by oncology pharmacy specialist and data manager].

BACKGROUND: S-1, an oral fluoropyrimidine, is one of the standard chemotherapeutic agents for the treatment of metastatic gastric cancer(MGC). However, the most effective second-line regimen after failure of treatment with first-line agents such as S-1 is yet to be determined. The aim of this study was to investigate the various second-line chemotherapy regimens in MGC patients. METHODS: We retrospectively studied patients with MGC who received second-line treatment after failure of the first-line S-1 or S-1/cisplatin treatment. The overall survival times with each second-line regimen were determined using the Kaplan-Meier method, and the effect on overall survival was analyzed using Cox regression analysis. RESULTS: The median survival time for all patients was 14. 2 months(95% confidence interval(CI): 12. 88-15. 43 months)with a 1-year survival rate of 60. 4%. Kaplan-Meier analysis revealed that the second-line regimens containing irinotecan significantly improved the median survival time as compared to regimens without irinotecan(median survival time: 16. 5 and 13. 8 months, respectively). Cox regression analysis showed that irinotecan-containing regimens were associated with improved overall survival(hazard ratio: 0. 165; 95% CI: 0. 041-0. 665). CONCLUSION: The use of irinotecan-containing regimens as second-line chemotherapy after failure of first-line S-1 therapy may be beneficial for MGC patients.

A case of pathological complete response of advanced rectal cancer to preoperative chemoradiotherapy using S-1.

In patients with advanced rectal cancer, preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy because of causing less toxicity and achieving higher rates of sphincter preservation and curative resection. We treated a patient who had advanced rectal cancer with preoperative chemotherapy using S-1 and concurrent radiotherapy. S-1 was orally administered at a dose of 100 mg/day during the first cycle (two-week on and one week off). During the third cycle, radiotherapy was initiated concurrently and a total dose of 45 Gy was given. The most severe adverse event was grade 3 leukopenia during the third cycle. On day 42 after completing radiotherapy, low anterior resection with diverting colostomy was performed. Histological examination found no viable cancer cells in the resected specimens, including the primary tumor site and lymph nodes. Thus, a pathological complete response was achieved. Postoperatively, anastomotic leakage occurred, but it was resolved with transanal drainage. Preoperative chemoradiotherapy using S-1 contributed to sphincter preservation and curative resection in this patient. This regimen was both effective and well-tolerated, suggesting that it could be useful for advanced rectal cancer.

Cases of two patients with aortoduodenal fistula who underwent emergency operation.

INTRODUCTION: Aortoduodenal fistula (ADF) is a rare but life-threating condition, and it is an important cause of massive gastrointestinal bleeding. Primary ADF often occurs as a result of aortic aneurysm, and secondary ADF develops after the placement of aortic prosthetic graft. PRESENTATION OF CASES: Case 1: A 64-year-old man with hematemesis was transferred to our hospital. The patient was diagnosed with primary ADF. Thus, we performed prosthetic graft replacement for an aortic aneurysm, and suturing of the duodenal fistula and duodenojejunal side-to-side anastomosis were performed. He was then discharged on the 35th postoperative day. After 2 years and 10 months, he died of other diseases. Case 2: A 76-year-old man with a history of abdominal aortic aneurysm repair with a prosthetic graft 5 years back who presented with hematemesis and melena was transferred to our hospital. The patient was diagnosed with secondary ADF, and an emergency endovascular aneurysm repair (EVAR) and suturing of the duodenal fistula were perfomed. He was transferred for rehabilitation purposes on the 108th postoperative day but eventually died of pneumonia 6 months after surgery. DISCUSSION: ADF is associated with high mortality. Initial bleeding is usually minor and often intermittent. However, it leads to severe bleeding and hemorrhagic shock. EVAR is preferred over open surgery because it can be performed faster and is less invasive. Recently, in case of hemorrhagic shock, EVAR is used as first-line treatment. CONCLUSION: Accurate diagnosis and immediate treatment are important for the survival of patients with ADF.

Calcification and abscess formation around the catheter tip of a central venous access port: a case report.

BACKGROUND: Thrombosis of the internal jugular vein occasionally occurs in association with long-term placement of a central venous catheter; however, such complications rarely involve calcification within the blood vessels. We report a case of calcification and abscess formation around a central venous catheter tip. CASE PRESENTATION: Our patient was an 84-year-old Asian woman who developed a fever that had started approximately 5 months after the placement of a central venous catheter. At the time of presentation, blood tests showed a marked inflammatory response, and chest computed tomography showed a high absorption area and air density around the catheter tip. Therefore, the patient was diagnosed with abnormal intravascular calcification and a deep neck abscess associated with long-term central venous catheter placement. The initial plan was to administer antibiotics and remove the central venous catheter. However, central venous catheter removal was deemed difficult due to the calcification and therefore required an incision. Because of the patient's advanced age and dementia, her family requested antibiotic treatment only. Following antibiotic treatment, the patient's inflammatory response normalized, and her fever resolved. The treatment was discontinued, and the patient's condition gradually stabilized. CONCLUSIONS: Catheter-related complications of central venous catheter placement include vascular occlusion, extravasation of the infusion, and infection. However, abnormal calcification in the blood vessels is extremely rare, and there has been only one case report of a neonate with central venous catheter-related vascular calcification in Japan. The etiology of intravascular calcification is considered to be related to the infusion content and the infusion rate of high caloric infusions and blood products. The incidence of complications associated with long-term central venous catheter placement is expected to increase with the increasing aging of the population and advances in chemotherapy. The report of the clinical course of this rare case adds to the body of knowledge in this area.

Significance of urinary glucaric acid measurement and its application to paclitaxel therapy.

Individual variations in P-450 activity affect the in vivo pharmacokinetics as well as the efficacy and side effect of drugs. It is proposed that urinary glucaric acid (GA) level may indirectly represent P-450 activity and may therefore be an indicator of P- 450 activity in the clinical setting. However, no standard method has been developed so far. Metabolism of paclitaxel (PTX), an anticancer drug, is mediated by P-450. If P-450 activity could be predicted by measuring urinary GA level during PTX administration and individual blood PTX concentration could be inferred, urinary GA level would be a potent tool to predict the efficacy and side effects of the drug. We therefore measured the urinary GA levels of patients on antiepileptics that are suggested to induce P-450 and those of control subjects, to determine whether urinary GA level could be an indicator of P-450 activity. Then, we examined the relationship between urinary GA level and blood PTX concentration and looked into the possibility of predicting pharmacokinetics based on the relationship between urinary GA level and area under the blood concentration-time curve (AUC). The means+/-S. D. of urinary [(GA level)/(Cr level) x 10] levels of 16 patients on antiepileptic medication and 24 control subjects were 0. 98 mg/mL+/-0. 91 and 0. 19 mg/mL+/-0. 07, respectively. The urinary GA levels of patients on antiepileptic medication were significantly higher than those of control subjects. On the other hand, the relationship between AUC and urinary GA levels in eight patients on PTX showed that AUC tended to become large when urinary GA levels were low. The above results reveal that measuring urinary GA level by the easy and noninvasive way of urine collection would enable us to predict P-450 activity and infer blood PTX concentration.

[Significance of urinary uracil measurement following administration of DPD inhibitory fluoropyrimidine(DIF)products].

Individual differences in 5-FU metabolism are mainly attributed to individual differences in the activity of DPD, an enzyme that can metabolize more than 85% of 5-FU. Because urinary uracil is a reflection of DPD activity, it is measured to predict and prevent the occurrence of side effects caused by pyrimidine-type chemotherapeutic agents. From urinary uracil values measured in 84 gastrointestinal cancer patients, 0-60 mmol/g.creatinine was set as a standard. In patients whose urinary uracil values exceeded the standard, 5-FU tended to be accumulated when S-1, a DIF product, was administered and side effects, such as anorexia, vomiting and diarrhea occurred immediately after the start of S-1 administration. If an appropriate DIF product is selected and its dosage set based on the patient's urinary uracil value, the occurrence of side effects would be reduced. Subsequently, a continuation of medication would be possible.

Individual differences in rate-limiting reactions during metabolism of irinotecan hydrochloride.

UNLABELLED: Irinotecan hydrochloride (CPT-11) is converted to SN-38 by carboxylesterase, SN-38 is conjugated by UDP-glucuronosyl- transferase (UGT) to SN-38G. Individual differences in enzyme activity influence the efficacy of this anticancer agent and the adverse reactions it induces. In this study, individual differences in the metabolism of this drug were determined by calculating its c 1 on version (CPT-11 to SN-38) and conjugation ratios (SN-38 to SN-38G) from blood concentrations of CPT-11, SN-38, and SN-38G at immediately and 60 min after a 90-min intravenous infusion of CPT-11. Changes in conversion and conjugation during long-term infusion of CPT-11 were also investigated. The median conversion and conjugation ratios were 0.0155 and 2.812, respectively (n=48). Based on these values, the patients were classified into four types: low-low type (10.4%), low-high type (31.2%), high-low type (31.2%), and high high type (27.1%). Prolongation of infusion time resulted in an increase in the conversion ratio in the low-high type and an increase in the conjugation ratio in the high-low type. These changes, however, were very slight in the high-high type. Thus, a longer infusion time made it possible to increase the number of doses in the low-high type and minimize adverse reactions in the high-low type. CONCLUSION: In patients found to have a low SN-38 conversion ratio or SN-38G conjugation ratio based on simple assessment of data obtained by 2-point blood sampling, modification of infusion time may allow pharmacokinetic changes that confer a clinical benefit.

Nonhepatocytic malignant mixed tumor of the liver in adults: report of a long surviving case.

A primary nonhepatocytic malignant mixed tumor in the liver contains both epithelial and mesenchymal components, and the incidence in adults is extremely rare. A 45-year-old female was admitted because of abdominal fullness. Abdominal imaging studies revealed a huge cystic tumor with a mural nodule in the right lobe. A right trisegmentectomy and an invaded partial diaphragm resection were performed. Diagnosis was established after surgery. The patient is still alive 11 years after surgery, and to our knowledge is the longest surviving patient with a primary nonhepatocytic malignant mixed primary tumor of the liver.

[Improvement of urinary d-glucaric acid assay and its application].

We propose an improved method to measure urinary D-glucaric acid (GA), which might be of value as an indirect index of the activity of cytochrome P450 (CYP). This method was about 20 times more sensitive than existing methods. Beer's law was obeyed in the concentration range 5.5-66 ng ml(-1) for GA, with the effective molar absorptivity at 533 nm and the relative standard deviation being 9.1 x 10(5) dm(3) mol(-1) cm(-1) and 0.69% (n = 6), respectively. In addition, we introduced the correction value {GA/Cr ratio x10} of urinary GA by measuring urinary creatinine (Cr) at the same time. Based on the proposed method, the GA and Cr values in spot urines of healthy persons and cancer patients were subsequently measured and the correction values of both groups subjected to comparison. As a result, a statistically significant difference was recognized between the two groups.

[Study of a relationship between a change in the urinary uracil value after a S-1 long-term administration and the recurrence of stomach cancer].

S-1 has been reported good results in the treatment of stomach cancer. However, a DPD activity change has also been reported as one of the causes for a recurrence though some recurrence cases observing a state of tumor being unchanged continuously for more than 1 year. Therefore the urinary uracil value, which could simply be predicted in the DPD activity at the time of a recurrence after having administered S-1 for a long-term, was measured. And the urinary uracil value was examined whether it could become an index of recurrence compared with a healthy 5-person example as reference. In the result, a monthly difference in change of the urinary uracil values of the reference was small. However, the urinary uracil values in patients who were administered S-1 more than 6 months but recurred, were significantly lower comparing with the healthy 5-person example. We concluded from this study that the change in DPD activity due to an induction of DPD by 5-FU and metastasis of cancer caused the recurrence and lower a urinary value. The urinary uracil value reflecting DPD activity of the whole body could be used as an index of recurrence at the time of long-term dosage of S-1. Furthermore, a measurement of the urinary uracil value seems to be promising for estimation and evaluation of the cure.

Laparoscopic gastropexy for chronic gastric volvulus.

Gastric volvulus is an infrequently encountered clinical entity characterized by abnormal rotation of the stomach. Surgical treatment by anterior gastropexy is indicated for acute and chronic gastric volvulus. Recently, laparoscopic surgery has been used in abdominal surgery. We report the case of a patient with chronic gastric volvulus who was treated by laparoscopic gastropexy and evaluated by upper gastrointestinal series and endoscopic appearance of the stomach. The laparoscopic approach is safe and effective for patients and is considered applicable to surgery for other upper gastrointestinal disorders requiring organ fixation.

Endoscopic microwave coagulation therapy of postoperative hemorrhage from a stapled anastomosis.

We experienced three cases of postoperative hemorrhage from a stapled gastrointestinal anastomosis, and established endoscopic microwave coagulation therapy (EMCT) with a cylinder-type electrode. We were able to treat postoperative hemorrhage over the entire circumference of stapled anastomosis successfully. Two patients had undergone a lower third thoracic esophagogastrectomy through a left thoraco-abdominal approach for gastric cancer in the cardia, while the other case had undergone Billroth I gastrectomy. They each had fresh bleeding from the stapled anastomosis after the operation. Emergency endoscopic examination was immediately performed. Endoscopy revealed bleeding on the suture line. We performed hemostasis endoscopically with microwave coagulation therapy safely. They were discharged from the hospital without complications such as leakage and stenosis. Since EMCT with the cylinder-type electrode can coagulate shallowly and widely, it is very effective for hemorrhage from a stapled anastomosis.

[Support of TS-1, 5-FU preparation containing potent DPD inhibitor by determination of urinary uracil/serum 5-FU clearance].

Though FU-derived anticancer agents are metabolized and detoxicated by dihydropyrimidine dehydrogenase (DPD), its wide distribution of activity is concerned primarily in the antitumor effects or side effects of 5-FU. In recent years, it has become possible to predict the metabolism of FU-derived anticancer agents by DPD activity through the determination of urinary uracil levels. In the present study, therefore, we examined whether or not urinary uracil levels could be used as a predictor for as certaining the efficacy and/or side effects of TS-1, which contains a potent DPD inhibitor. Consequently, the following relationship was revealed to exist between urinary uracil levels and clinical effects of TS-1: 1) The effect of TS-1 administration was generally good in patients whose uracil level was within the standard values with no presentation of serious side effects. 2) The administration of TS-1 was also useful even in patients whose uracil levels were below the standard value. 3) Though no side effects were observed when a conventional FU-derived anticancer agent was administered to patients showing an urinary uracil level below the standard value, some side effects appeared when TS-1 was administered. Under present circumstances where understanding of genome diagnosis and establishment of informed consent are rather difficult, this approach of predicting DPD activities through the determination of urinary uracil levels seems to be of help for deciding a therapeutic regimen based on the patient's constitutional features when a cancer chemotherapy with TS-1 is performed.

[Combined determination of urine uracil levels and plasma 5-FU clearance for a simple order-made treatment with anticancer agents of FU derivative].

Individual differences exist in the pharmacodynamics of fluorouracil-derived anticancer agents, with circadian variability even in the same patient probably due to individual differences in the distribution of dihydrophrimidine dehydrogenase (DPD), a decomposing enzyme. Though DPD activity is usually determined in the liver or blood, a more simplified estimation of DPD activity has been recently attempted using urine uracil levels. However, because urine uracil level has the drawback of being easily affected by food ingestion or kidney function, in this study it was determined simultaneously with the determination of plasma 5-FU clearance after sustained instillation of 250 mg 5-FU, in order to estimate DPD activity more accurately. A correlation was observed between urine uracil levels and 5-FU clearance. In cases showing a baseline urine uracil level below 25.1 mumol/g. Creatinine, the blood concentration decreased due to large 5-FU clearance, with a tendency for diminished efficacy of FU-derived anticancer agents. In cases showing a baseline urine uracil level above 99.9 mumol/g. Creatinine, on the other hand, adverse reactions due to FU anticancer agents tended to become more serious. Since urine uracil level can be determined easily, it could be the first choice in screening to detect abnormal metabolism of fluorouracil-derived anticancer agents under present circumstances. By combining determination of urine uracil level with 5-FU clearance, it seems possible to predict adverse effects and the effective rate of these agents more accurately. Under existing circumstances, where genetic analysis remains unavailable as a general practice, the combined determination of urine uracil levels and plasma 5-FU clearance may be beneficial in developing order-made treatments in cancer chemotherapy.