[Three Cases of Appendiceal Goblet Cell Adenocarcinoma in Our Institution].

Appendiceal goblet cell adenocarcinoma(AGCA)is a newly designated pathological term adopted in the 5th edition of the WHO classification. It is synonymous with goblet cell carcinoid, which was previously categorized as a part of appendiceal carcinoid. However, since 2018, it has been classified as a subtype of adenocarcinoma. We have experienced 3 cases of this relatively rare tumor, of which 2 were initially diagnosed with acute appendicitis and were diagnosed with AGCA by pathological examination after an emergency appendectomy. Each of them underwent additional ileocolic resection with lymph node dissection as the second surgery. In the 3rd case, an appendiceal tumor was detected during preoperative examinations for an ovarian tumor. Staging laparoscopy revealed comorbid peritoneal dissemination, and only the appendix and right ovary were removed in the consecutive surgery. The ovarian tumor was pathologically diagnosed as a metastasis of AGCA. In this case, the introduction of oxaliplatin-based systemic chemotherapy after surgery achieved a complete response after more than 2 years. Although no recurrence has been observed in all 3 cases to date, AGCA is considered highly malignant compared to conventional appendiceal carcinoids. Therefore, it is crucial to practice multidisciplinary treatments, including sufficient radical surgery based on a precise diagnosis of AGCA, as is performed for advanced colorectal cancer.

[A case of CA19-9-producing esophagogastric junction cancer with ovarian juvenile granulosa cell tumor and rectal cancer].

This is a report on a case of CA19-9-producing cancer of esophagogastric junction with rectal cancer and a suspicion of Krukenberg tumor, a metastasized ovarian tumor that would mean an inoperable condition of cancer progression if that were true. This was a case of a woman in her 60s who was diagnosed with double cancers at the esophagogastric junction and rectum with a swollen left ovary. She had a laparoscopic bilateral salpingo-oophorectomy to get a histologic diagnosis, which should affect the subsequent therapeutic strategy because metastasis to the ovary meant an inoperable cancer progression. The resected ovary was diagnosed as juvenile granulosa cell tumor, but not Krukenberg tumor. Thus, subsequent curative surgeries, such as thoracolaparotomy for esophagogastric junction cancer and robot-assisted surgery for rectal cancer, were performed. Immunohistochemical examination revealed that the expression of CA19-9 was strongly observed in the tumor of esophagogastric junction, but not in the tumors of rectum or ovary. Furthermore, serum CA19-9 was drastically decreased after the resection of esophagogastric junction cancer. In aggregate, this esophagogastric junction cancer met the criteria of CA19-9-producing gastric cancer defined by Okinaga et al. So far, 46 cases of CA19-9-producing gastric cancer including this case have been reported in Japanese literature. Interestingly, this case had another characteristic of juvenile granulosa cell tumor, one of borderline malignant sex cord-stromal tumors rarely found in adults.

[Three Cases of Colon Medullary Carcinoma in Our Institution].

Medullary carcinoma of the colorectum is a relatively new histological subtype that was first described in the eighth edition of the Japanese classification of colorectal, appendiceal, and anal carcinoma. In our institution, only 3 cases of medullary carcinoma have been diagnosed since 2013. Case #1 was a 93-year-old woman with type 1 ascending colon cancer; she received a right hemicolectomy. The tumor invaded the subserosal layer, but no lymph nodal metastasis was observed. Case #2 was a 91-year-old woman with obstructive ascending colon cancer. After intracolonic decompression using the transnasal ileus tube, she received a right hemicolectomy. This tumor also extended into the subserosal layer without lymph nodal metastasis. Case #3 was a 65-year-old woman with a family history of cancers; she received a right hemicolectomy for cecal cancer with an aberrant elevation of serum tumor markers such as CEA and CA19-9. The tumor invaded the subserosal layer with regional lymph nodal metastases. Notably, these 3 cases were females who had right-sided tumors and all showed diminished expressions of MLH1 and PMS2 mismatch repair-associated genes, together with epidemiological characteristics of medullary carcinoma. Herein, we report their pathological features along with the corresponding literature review.

Contrast-enhanced ultrasonography combined with superb microvascular imaging for preoperative diagnosis of sporadic intra-abdominal desmoid-type fibromatosis: A case report.

We herein report a case of sporadic intra-abdominal desmoid-type fibromatosis in which contrast-enhanced ultrasonography (US) combined with superb microvascular imaging (SMI) was useful for preoperative diagnosis. 18-Fluorodeoxyglucose positron emission tomography performed for systematic screening for lung cancer revealed an abnormal accumulation in the abdominal cavity. Transabdominal US showed a tumor with a mixture of hypoechoic and hyperechoic areas. Contrast-enhanced US combined with SMI revealed dendritic blood flow signals and no abnormal vascular network within the tumor. Macroscopic examination of the resected specimen revealed a white tumor with relatively clear boundaries. Microscopic examination revealed spindle cells with poor atypia proliferating in bundles with collagenous stromal cells. Immunohistochemistry showed nuclear localization of beta-catenin within the tumor cells. From these findings, we finally diagnosed intra-abdominal desmoid-type fibromatosis. Contrast-enhanced US combined with SMI is useful for diagnosing intra-abdominal desmoid-type fibromatosis.

Appendiceal mucocele pathologically classified as appendiceal epithelial hyperplasia and preoperatively diagnosed by contrast-enhanced ultrasonography: A case report.

We report a patient with a mucocele with diffuse wall thickening diagnosed by transabdominal ultrasonography and contrast-enhanced ultrasonography. Transabdominal ultrasonography showed diffuse thickening of the entire appendix wall and an anechoic area that appeared to be fluid collected throughout the appendix lumen. However, the "onion skin sign" was not detected. Contrast-enhanced ultrasonography combined with superb microvascular imaging revealed abundant mucosal blood flow and no abnormal vascular network within the mucosa of the appendix wall. We preoperatively diagnosed a mucocele complicated by acute and chronic appendicitis, and ileocecal resection was performed. Macroscopic and microscopic findings of the resected specimens demonstrated that the appendiceal wall was diffusely thickened, with fibrosis and inflammatory cell infiltration, and that the appendiceal root rumen was narrowed with epithelial hyperplasia. No neoplastic changes were observed. The cause of the appendiceal mucocele was likely fibrosis and stenosis at the root of the appendix due to initial acute appendicitis.

Minimally invasive surgery using intraoperative real-time capsule endoscopy for small bowel lesions.

BACKGROUND: The small bowel has been considered the "black box" of gastroenterology. Identifying the exact site of small bowel hemorrhage is often difficult, thus complicating surgical treatment. We report two cases of small bowel bleeding lesions that were successfully managed by intraoperative real-time capsule endoscopy and minimally invasive surgery. METHODS: We developed a double-lumen tube similar to, but thinner and longer than, the Miller-Abbott tube. We insert the tube nasally, 3 or 4 days preoperatively, such that its balloon tip reaches the anus by the operative day. During surgery, the endoscopic capsule is connected to the balloon tip of the tube that protrudes from the anus. An assistant pulls on the nasal end of the tube, bringing the balloon tip and capsule back into the bowel. Capsule endoscopic images are displayed in a real-time video format. RESULTS: We employed this procedure in two patients with repeated melena. Various examinations including gastroendoscopy and total colonoscopy showed bleeding confined to the small bowel, but the exact lesion site was unknown. Minimally invasive surgery was successfully performed in both patients: open minilaparotomy in one and laparoscopy in the other. The small bowel and capsule endoscope were easily controlled during minilaparotomy, and real-time capsule endoscopic images clearly identified the bleeding lesion. Control of the small bowel was more difficult in the laparoscopic case; however, real-time capsule endoscopic images identified a small tumor that was successfully resected. CONCLUSIONS: Intraoperative capsule endoscopy combined with the tube provides surgeons real-time images indicating the exact site of lesions. The tube also helps surgeons control the position of the capsule endoscope and enables suction of intraluminal fluid or inflation of the lumen to allow clearer views during the operation. We conclude that combined use of capsule endoscopy and the tube facilitates management of bleeding lesions in the small bowel.

[Results of hepatic arterial infusion chemotherapy with 5-FU and leucovorin for unresectable liver metastases from colorectal cancer].

PURPOSE: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer. METHODS: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0. RESULTS: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure. CONCLUSION: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.

[A resected case of postoperative liver metastasis of a gastrointestinal stromal tumor showing complete response after imatinib treatment].

A 71-year-old man visited the hospital complaining of nausea in December 2002. Following a diagnosis of a gastrointestinal stromal tumor (GIST), partial resection of the stomach was performed in January 2003. The tumor was immunohistochemically positive for c-kit and CD34. The tumor size was 6.5 x 5.0 x 4.5 cm with a mitotic index of 25 out of 50 in the high-power field. The pathological diagnosis indicated a high-risk GIST. Treatment with imatinib at a dose of 400 mg/day was started because of liver metastasis of the GIST in January 2004. The liver metastasis was gradually reduced and exhibited cystic change. We considered that there was a complete response without accumulation by FDG-PET in June 2007. An hepatic segmentectomy was performed and imatinib was discontinued in July 2007. Most intratumorale in the specimen underwent hyaline degeneration after pathological examination, but there were viable cells in a portion of the tumor border. Imatinib treatment was resumed because of recurrence in the remnant stomach four months postoperatively owing to imatinib withdrawal. In making a diagnosis at the cell level by FDG-PET, it was difficult to determine the effectiveness of imatinib, and therefore, it is suggested that imatinib treatment must be continued after surgical resection.

Descending necrotizing mediastinitis in a healthy young adult.

A 26-year-old man with right lower mandibular and chest pain, fever, and respiratory distress was urgently transported to our hospital. CT images revealed gas collection and an abscess from the neck to the mediastinum with bilateral pleural effusion. Descending necrotizing mediastinitis (DNM) induced by an odontogenic infection of a right mandibular molar abscess was diagnosed. The cervical and mediastinal areas were drained, extensive debridement was performed, necrotic tissue was excised, and broad-spectrum antibiotics were administered immediately. Prompt diagnosis and intensive care were necessary for managing the DNM, and the patient was discharged with no comorbidities.

[A feasible study of docetaxel/nedaplatin combined chemotherapy for relapsed or refractory esophageal cancer patients as a 2nd-line chemotherapy].

As a 2nd-line treatment for relapsed or refractory esophageal cancer patients after chemoradiotherapy, we performed a combination chemotherapy of DOC/CDGP for 11 patients. Intravenous drip infusion of DOC 30 mg/m(2)and CDGP 30 mg/m(2)on days 1, 8 and 15, and 4 weeks treatment was assumed as 1 cycle. We treated 8 of 11 patients with more than 2 cycles, and 4 of 8 patients were treated with radiation therapy (RT). The effects by RECIST revealed partial response (PR) in 2 patients (50%), stable disease (SD) in 1 patient and progress disease (PD) in 1 patient without RT, and PR in 3 patients and not effective in 1 patient with RT, respectively. There was no treatment-related death nor adverse event of grade 4. The Hematological toxicities of leukopenia of grade 3 were observed in 3 patients. Non-hematological toxicites more than grade 3 were not observed. The combination chemotherapy of DOC/CDGP was concluded to be safe and effective for relapsed or refractory esophageal cancer patients as a 2nd line treatment.

[Pharmacokinetics of 5-FU after S-1 oral administration for adjuvant chemotherapy in gastric cancer patients].

We studied the pharmacokinetics of 5-FU after S-1 oral administration at the usual dose (80 mg/m2) for adjuvant chemotherapy in 13 advanced gastric cancer patients (Stage II, III), and at a decreased dose (60 mg/m2) for adjuvant or combined chemotherapy in 13 advanced gastric cancer patients. Pharmacokinetic parameters of 5-FU in the serum were as follows: Cmax, 159 .9 2+/-45.2 ng/mL, Tmax, 2.17+/-0.58 h;T1/2, 3.13+/-2.88 h; and AUC(0-8), 768.0+/-260.8 ng h/mL in the patients with the usual dose, and Cmax, 117.3+/-55.1 ng/mL; Tmax, 2.62+/-0.9 6 h; T1/2, 3.09+/-1.9 5 h and AUC(0-8), 565.9+/-216.8 ng h/mL in the patients with the decreased dose. No difference in AUC was observed between operative methods. Adverse events of more than grade 3 were recognized in 7 patients, and AUC of 6 patients were more than 800 ng h/mL. The plasma concentration of 5-FU was quite different between patients. The difference of Cmax and AUC was 3-4 times. It was concluded that we must pay attention to individual differences in the plasma concentration of 5-FU in postoperative gastric cancer patients when S-1 would be administered.

[Pyogenic liver abscess complicated by gastric fistula and bacterial meningitis].

A 77-year-old woman was admitted suffering from fever and headache. On laboratory examination, bacterial meningitis and sepsis due to Klebsiella pneumoniae were diagnosed. In addition, a hepatic cystic lesion measuring 13 cm in diameter in the left lobe was indicated on diagnostic imaging. After treatment with antibiotics, her signs of infection improved and the hepatic lesion decreased in size. After discharge, however, the cystic liver mass increased and a gastric fistula developed. Hepatic and gastric resections were performed because of the possibility of biliary cystadenocarcinoma and gastric invasion. Pathologically, a pyogenic liver abscess complicated by gastric fistula was diagnosed.

False-Positive Cases of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomographic Scans in Metastasis of Esophageal Cancer.

Of 129 esophagectomies at our institute from June 2010 to March 2015, we experienced three preoperative positron emission tomography-computed tomographic (PET/CT) false positives. Bone metastasis was originally suspected in 2 cases, but they were later found to be bone metastasis negative after a preoperative bone biopsy and clinical course observation. The other cases suspected of mediastinal lymph node metastasis were diagnosed as inflammatory lymphadenopathy by a pathological examination of the removed lymph nodes. Conducting a PET/CT is useful when diagnosing esophageal cancer metastasis, but we need to be aware of the possibility of false positives. Therapeutic decisions should be made based on appropriate and accurate diagnoses, with pathological diagnosis actively introduced if necessary.

[A phase I/II study of docetaxel/TS-1 with radiation for esophageal cancer patients--step 1].

The therapy 5-FU and CDDP with radiation is thought to be the standard therapy for esophageal cancer patients by now. However, the therapy is associated with a comparatively high incidence of gastrointestinal disorders and requires hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with radiation for maintaining of QOL and improving outcome. Step 1 of the clinical phase I/ II study was conducted for 10 cases from May 2004 to March 2006. Treatment could be accomplished in all cases, and no treatment-related deaths or adverse events of grade 4 were observed in any case. As for hematotoxicity, one case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic adverse events, anorexia of grade 3 was recognized in one case of level 3. The response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases), and the rate based on the Guide Lines for the Clinical and Pathologic Studies on Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30 mg/m(2) and that of TS-1 was 60 mg/m(2) with radiotherapy of 60 Gy. This combination therapy may be recommended because of fewer adverse events and a higher responsive rate than the standard therapies. We intend to continue this study to step 2 and 3, and to reveal the response rate and adverse events for more esophageal cancer patients.

Surgical oncotaxis--excessive surgical stress and postoperative complications contribute to enhancing tumor metastasis, resulting in a poor prognosis for cancer patients.

We investigated the relationship between surgical stress and tumor metastasis. The excessive surgical stress of a thoracolaparotomy enhanced tumor metastasis remarkably in an experimental model. We would like to propose that this phenomenon be termed "surgical oncotaxis". This effect has previously been attributed to some mechanisms of immunosuppression, excessive secretion of corticoids, and active oxygen production of granulocytes. An increase in lipid peroxide (LPO) in the liver was observed after a thoracolaparotomy, but a strong radical scavenger of a DL-alpha-tocopherol-L-ascorbic acid 2-0-phosphate diester (EPC-K1) restrained LPO levels in the liver and the effect of tumor metastasis in parallel. As clinical strategies for restraining the surgical oncotaxis, the control of any cytokine storm after surgery and/or the scavenging of active oxygen appears to be possible and hopeful, since it might be intermediated by cytokine. When pre-administration findings for EPC-K1 and methylpredonisolone were compared, EPC-K1 was found to be more suitable for restraining surgical oncotaxis, because serum LPO was only controlled with EPC-K1. The cytokine storm which occurs after surgery is augmented by a second stimulation, such as the administration of lipopolysaccharide, and no drug could control this well experimentally. Postoperative complications are a clinical model of a second stimulation (a so-called second attack). Our data showed the prognosis of a group with complications to be worse than that of a group without them even though no difference existed in the background of the esophageal cancer patients studied. Based on these results, safe surgery and the choice of minimally invasive surgery are the best ways to control surgical oncotaxis. Following a major surgical procedure, such as a thoracolaparotomy, the use of corticoids and/or radical scavengers can contribute to restraining surgical oncotaxis.

Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest.

In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer.

Gender differences in the dihydropyrimidine dehydrogenase expression of colorectal cancers.

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5-FU). DPD expression levels are believed to correlate with the 5-FU sensitivity of malignant tumors. In colorectal cancer (CRC), a few previous studies demonstrated that females could benefit more from adjuvant chemotherapy. However, it is still unknown why the effectiveness of postoperative chemotherapy is affected by gender. The objective of this study was to clarify the beneficial differences in 5-FU chemotherapy between genders in patients with the CRC based on DPD expression. Ninety-seven tumor specimens and 92 adjacent normal tissue specimens from 97 patients with the CRC and no prior therapy were obtained. The DPD expression in the tissues was quantified and analyzed based on clinicopathological factors. In the tumor tissue, the DPD expression in females was significantly lower than that in males. In the normal tissues, however, there were no significant differences in DPD expression between genders. In the treatment of CRC, cases who will benefit most because of 5-FU sensitivity; i.e. cases with lower DPD expression, must be given priority. Based on DPD expression, female gender seems to be a predictive factor for a better response to chemotherapy with 5-FU.

Double common bile duct: a case report and a review of the Japanese literature.

BACKGROUND: A double common bile duct (DCBD) is a rare congenital anomaly. We report the case of a 60-year-old Japanese female, whose common bile duct divided into 2 channels and both channels opened individually into the second portion of the duodenum. This is the fourth reported case of DCBD with a choledochal cyst and pancreaticobiliary maljunction (PBM). METHODS: A review of the literature revealed that DCBD is more frequently diagnosed in Oriental people. We reviewed 47 cases of DCBD reported in the Japanese literature. RESULTS: Among these, cholelithiasis was found in 27.7%, a choledochal cyst in 10.6%, PBM in 29.8%, and cancers in 25.5%. Cancer and PBM were the 2 most serious concomitant conditions. The incidence and type of complicating cancer and PBM varied according to the site of the opening of the accessory common bile duct (ACBD). Concomitant gastric cancer was frequently noted when the ACBD opened into the stomach, whereas cancer of the biliary system was common when the ACBD opened into the second portion of the duodenum or the pancreatic duct. PBM was observed only in those patients in whom the ACBD opened into the second portion of the duodenum or the pancreatic duct. Therefore the treatment and prognosis of DCBD is influenced by the site of opening of the ACBD. CONCLUSIONS: In DCBD, the opening site of the ACBD was considered to have close implications for the type of concomitant cancer and concomitant PBM that would appear.

First jejunal vein oriented mesenteric excision for pancreatoduodenectomy.

BACKGROUND: Dissection of the pancreatic head from the superior mesenteric vein (SMV) and artery (SMA) are major points of bleeding in pancreaticoduodenectomy (PD) because of congestion of the pancreatic head. The "SMA-first" approach, which involves ligating the artery from the SMA first, can be used to solve this problem. However, the SMA-first approach has problematic anatomical issues. We applied a new surgical approach, first jejunal vein oriented mesenteric excision (FME), for PD. This study aimed to clarify the effect of FME on reduction of bleeding during PD. METHODS: The jejunal vein, the most frequent source of bleeding during dissection of the mesoduodenum, was identified at the beginning of dissection of the pancreatic head from SMV and SMA. The mesoduodenum, including plural IPDAs, was completely divided before dissection of the pancreatic head from the SMV. The perioperative outcomes of two groups, patients who underwent FME-based PD and patients who underwent standard PD, were compared. Additionally, the spatial characteristics of the first jejunal vein (FJV) were analyzed using computed tomography. RESULTS: FME-based PD significantly reduced intraoperative blood loss compared with conventional PD (569 vs. 1094 ml, P = 0.0315). The median distance of the FJV was 0 mm from the middle colic artery and 0 mm from the third portion of the duodenum. The FJV was posterior to the SMA in the majority of the patients but was anterior to the SMA in 16.7 % of patients. CONCLUSIONS: FME is useful for reducing intraoperative bleeding.