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PURPOSE The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899 ). PATIENTS AND METHODS Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients’ registration. RESULTS Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P < .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum ( P < .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

The patient was a 79-year-old man. He underwent endoscopic papillectomy for ampullary cancer when he was 70 years old. At the ages of 71 and 73 years, liver metastasis in segment 6 was detected, and radiofrequency ablation(RFA)was performed and adjuvant chemotherapy(gemcitabine, S-1)was administered. At the age of 79 years, recurrence of liver metastasis appeared. Because there were no other metastatic lesions, we performed S6 subsegmentectomy. Five months after the surgery, no recurrence was observed. In general, the prognosis of patients with ampullary cancer with distant metastasis is very poor. This case suggested the efficacy of multidisciplinary treatment, including surgery, RFA, and chemotherapy, in a patient with ampullary cancer with distant metastasis.

Metastasis of renal cell carcinoma to the pancreas is a relatively rare condition. We encountered 2 such cases. The first case was a 72-year-old man who underwent a left nephrectomy owing to left renal cancer in 2005. An abdominal dynamic CT scan 12 years after surgery revealed tumors in the pancreatic body and right kidney. A PET-CT scan revealed low intensity uptake of both tumors, and therefore, metastasis of the left renal cell carcinoma to the pancreas was suspected. We then performed partial resections of the pancreatic tail and right kidney. Pathologic findings confirmed that the pancreatic tumor and right renal tumor were metastases of the left renal cell carcinoma. The postoperative course was favorable, and the patient has been followed up in an outpatient setting for 10 months with no signs of recurrence. The second case was a 51- year-old woman with tumors in the left kidney and pancreatic head that were detected by abdominal contrast CT and MRI. We diagnosed the patient with left renal cell carcinoma with metastasis to the pancreas. We performed a radical nephrectomy of the left kidney and full pancreatectomy. Pathologic findings confirmed left renal cell carcinoma, pStage Ⅳ, with metastasis to the pancreas. The postoperative course was favorable without recurrence for 14 years. We report on two cases of metastasis of renal cell carcinoma to the pancreas in patients who underwent radical resections and had favorable postoperative courses, with some bibliographic consideration.

A 67-year-old woman was diagnosed with rectal cancer using colonoscopy. Computed tomography revealed the so-called superior mesenteric vein rotation sign, and intestinal malrotation was suspected. We planned chemotherapy after the surgical resection of the primary cancer because she had multiple lung metastases. Laparoscopic high anterior resection with D3 dissection of lymph nodes was performed. Intraoperative findings showed a non-rotation type intestinal malrotation and severe intra-abdominal adhesion. However, careful releasing operation enabled the typical approach of laparoscopic surgery for rectal cancer. The postoperative course was generally good, and she was discharged on the 17th postoperative day. The pathological diagnosis was rectal cancer(T3, N0, M1a, pStage Ⅳ). In laparoscopic surgery for colorectal cancer with intestinal malrotation, determining the anatomy of blood vessels and the site of the tumor before surgery is important. Furthermore, awareness that some cases have severe intra-abdominal adhesions even without a history of laparotomy is necessary.

A 70-year-old man was referred to our hospital and admitted after abdominal computed tomography(CT)examination revealed a tumor in the retroperitoneum. The specific blood test findings were poor, and surveillance CT demonstrated a wellcircumscribed, enhanced mass measuring 40mm with calcification behind the horizontal portion of the duodenum. The tumor presented with a slightly high signal in low signal, T2 in T1, and it showed a diffusion decrease in DWI; the simple abdominal MRIrevealed heterogeneous accumulation of SUVmax 3.0 only for the lesion in FDG/PET-CT. Specific findings did not lead to a diagnosis, although EUS-FNA lower aspiration biopsy cytology was performed. Laparoscopic tumorectomy was performed to help determine the treatment strategy. Histopathological examination indicated that the tumor was composed of multiple lymph follicles with concentric layers of mantle zone cells, showing an onion skin-like lesion and atrophic germinal centers. The germinal centers had penetrating arterioles with hyalinized vessel walls, and Castleman's disease(hyaline vascular type)was therefore diagnosed. In this case, it was difficult to diagnose Castleman's disease before surgery. Surgical excision is a diagnostic as well as a curative method for management of this disease.

We report 2 resected cases of patients with non-isolated splenic metastasis of colon cancer. Case 1: A 67-year-old man who underwent partial transverse colectomy and partial hepatectomy for transverse colon cancer and liver metastasis. Approximately 18 months after the operation, splenectomy and partial hepatectomy were performed for metastasis to the spleen and liver. After partial hepatectomy for another recurrence, no signs of new recurrence have been observed for 42 months after splenectomy. Case 2: A 53-year-old woman who presented with bloating. CT and MRI scans revealed masses of the ileocecum, both ovaries, and spleen. We performed right hemicolectomy, total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymphadenectomy, para-aortic lymphadenectomy, omentectomy, and splenectomy. Histological findings showed cecal cancer metastasizing to the bilateral ovaries and spleen. Metastatic splenic tumor is relatively rare(0.3-7.3%). Splenectomy was reported to be an effective treatment modality for isolated splenic metastasis, while that for non-isolated metastasis is uncertain. Surgical resection should be considered even in non-isolated splenic metastasis cases because of the evidence of long-term survival in case 1.

We report a patient with brain metastasis of rectal cancer who underwent metastatic tumor resection 3 times. In March 2012, a 76-years-old man, diagnosed with Stage III a rectal cancer, underwent Hartmann's operation. The lung metastasis was confirmed in July and November 2013, surgical resection for pulmonary metastasis was performed 2 times. In January 2016, he had difficulty of speaking, and isolated brain tumor was found. We performed surgical resection of brain metastasis in February 2016. In March and July 2016, the gamma knife radiosurgery was performed for other brain metastasis. In July 2016, he occurred nausea, headache and right identity hemi-blindness. Two new brain tumors were revealed. We performed surgical resection again. Three months after second brain surgery, he had dysarthria and a solitary brain tumor was confirmed. We performed third neurosurgical resection. All tumors of brain were found to be metastasis from rectal cancer in histological study. Currently, 16 months have passed since the first diagnosis of brain metastasis of this patient, and the quality of life was good relatively. The prognosis of the patients with brain metastasis is poor generally. However, this case suggested that multiple surgical resection of brain metastasis could improve prognosis and quality of life of patients. Accumulation of further cases is needed.

The patient was a 66-year-old woman, who was diagnosed with cT3N3M0, cStage III esophageal cancer with widespread lymph node metastases in the mediastinum and abdomen. She was treated with 2 courses of chemotherapy with docetaxel/ cisplatin/5-FU(DCF therapy). CT and FDG PET-CT showed a significant reduction in both the primary tumor and the metastatic lymph nodes following treatment. We performed subtotal esophagectomy and gastric tube reconstruction with lymphadenectomy. The histopathological findings showed no residual viable tumor cells or foreign body-type giant cells with necrosis. The pathological effect of chemotherapy was defined as Grade 3(pCR). Our case suggested that DCF chemotherapy is potentially a very effective treatment for advanced esophageal cancer with widespread lymph node metastases.

We report 2 cases of systemic steroid therapy for hyperbilirubinemia after right hepatic lobectomy for liver metastases from colorectal cancer.One of the patients was a 65-year-old man, diagnosed with transverse colon cancer with multiple liver metastases.After surgery for the primary lesion and chemotherapy(FOLFOX plus bevacizumab, FOLFIRI plus panitumumab), he underwent right hepatic lobectomy for the liver metastasis.His preoperative ICG 15 min was 8%.Conjugated hyperbilirubinemia without biliary stenosis occurred after the hepatectomy.Two courses of pulse steroid therapy were effective for only a limited period.After initiation of oral prednisolone therapy, his hyperbilirubinemia decreased.The other patient was a 66- year-old man with rectal cancer who underwent a low anterior resection.Postoperatively, a liver metastasis appeared.After CapeOX therapy, he underwent right hepatic lobectomy.His preoperative ICG 15 min was 5%.Conjugated hyperbilirubinemia occurred after hepatectomy.Pulse steroid therapy was effective for only a limited period.After initiation of prednisolone therapy, his hyperbilirubinemia decreased.In both cases, fatty changes in the liver were detected.Chemotherapy -associated hepatotoxicity may induce hyperbilirubinemia after hepatectomy.The effectiveness of systemic steroid therapy for hyperbilirubinemia is demonstrated by these cases.

The objective of this study was to investigate the clinicopathological features and postoperative survival of primary colorectal signet-ring cell carcinoma.Nineteen patients with primary colorectal signet-ring cell carcinoma were identified from a database of 5884 surgical patients with colorectal cancers treated surgically at Osaka University Hospital and affiliated hospitals between 1993 and 2007. The clinicopathological data of those patients were compared with those of 5792 patients with non-signet-ring cell colorectal carcinoma (5417 with well or moderately differentiated adenocarcinoma and 375 with poorly differentiated adenocarcinoma or mucinous carcinoma).All patients showed a tumor depth of over T3. Lymph node involvement occurred in 14 patients. Seven of 19 patients presented with distant metastasis at the time of diagnosis. The overall 5-year survival rate in primary signet-ring cell carcinoma was significantly lower at 24.1%, in comparison to 77.5% in well or moderately differentiated adenocarcinoma and 57.7% in poorly differentiated adenocarcinoma or mucinous carcinoma. Likewise, the postoperative survival in Stage III was also significantly worse. On the other hand, no significant difference was observed in Stage II or IV.The most important feature of primary colorectal signet-ring cell carcinoma is the advanced stage at the time of diagnosis. In addition, the postoperative survival is worse than for other types of colorectal cancer.

Widespread application of laparoscopic cholecystectomy (LC) has resulted in a high complication rate and leads to prolonged hospital stays. This study aimed to investigate the preoperative and intraoperative clinical factors that relate to prolongation of hospital stay.We studied 370 patients who underwent LC for gallbladder disease between 2008 and 2012. Clinical risk factors were retrospectively collected. The clinical pathway for LC was indicated for all patients, and they were divided into two groups according to postoperative length of stay (LOS): the normal duration group (LOS ≤5 days) and the long duration (LD) group (LOS ≥6 days). Multiple regression analysis was used to predict risk factors that identified hospital prolongation to create a LOS prediction score.The normal duration group was 236 patients and the LD group was 134. Seventeen patients (4.6%) required conversion from laparoscopic to open surgery. LOS was 4.82 days in the normal duration group and 12.08 days in the LD group. In the LD group, 18.7% of the patients stayed more than 14 days, but no patients were readmitted. Thirteen clinical factors were statistically different between the two groups. ASA score and LC difficulty were the most predictive risk factors for LOS prolongation. LOS prediction score consisted of eight variables selected from 13 factors; it helped determine the likelihood of whether a patients' hospital stay was prolonged (sensitivity, 82.1%; specificity, 75.0%).Thirteen factors closely related to hospital stay duration and LOS prediction score could predict the prolongation of a patient's hospital stay.

Objective: Combined chemotherapy with S-1 and irinotecan (IRIS) for metastatic colorectal cancer has been reported to be effective and safe. However, there are only a few studies on the effects of adding bevacizumab to IRIS. We conducted a clinical study to evaluate the efficacy and safety of IRIS plus bevacizumab as first-line therapy for metastatic colorectal cancer. Methods: Forty metastatic colorectal cancer patients were enrolled in this phase II study. All patients received irinotecan (80 mg/m2) and bevacizumab (7 mg/kg) on days 1 and 15 and S-1 (40-60 mg twice daily) on days 1-21 of a 5-week repeated cycle. Results: The response rate was 47.4% [95% confidence interval (CI) 31.5-63.2], progression-free survival was 11.9 months (95% CI 9.4-16.8), and overall survival was 23.4 months (95% CI 19.0-inf). The only grade 3 hematological toxicity was neutropenia (16%) and the incidences of grade 3 nonhematological toxicity were low at Conclusion: In this clinical study, we revealed IRIS plus bevacizumab to be a promising first-line regimen for metastatic colorectal cancer with a low incidence of serious toxicities, in which favorable response rates and extension of survival time can be expected.