Adjuvant Chemotherapy after Neoadjuvant Chemotherapy and Long-term Outcomes of CAPOX Plus Bevacizumab Followed by TME for High-risk Localized Rectal Cancer.

OBJECTIVES: We previously reported the feasibility of neoadjuvant capecitabine and oxaliplatin plus bevacizumab as a treatment for locally advanced rectal cancer (UMIN000003219). The aim of this study is to investigate the prognostic relevance of neoadjuvant chemotherapy followed by total mesorectal resection (TME). METHODS: Twenty-five patients of our prior multicenter prospective study of neoadjuvant chemotherapy followed by TME enrolled to this study. We analyzed the adjuvant chemotherapy regimen, and the duration between surgery and initial chemotherapy treatment. Five-year progression-free survival and overall survival were estimated using the Kaplan-Meier method. RESULTS: Among survivors, the median follow-up time was 66 months. Recurrence occurred in six patients, all of whom had suboptimal tumor regression after neoadjuvant chemotherapy. Five patients died from other causes. The rate of local recurrence and distant metastasis was 17.4% and 8.7%, respectively. Five-year progression-free survival was 70.0%, and 5 year overall survival was 84.0%. CONCLUSIONS: We report the long-term survival of patients who received neoadjuvant chemotherapy without radiation followed by TME, revealing a generally favorable prognosis.

[A Case of Castleman's Disease with Lymphadenopathy during the Treatment of Gastric Cancer].

We report a patient who had Castleman's disease with lymphadenopathy during the treatment of gastric cancer. In May 2017, a 63-year-old man underwent gastrointestinal endoscopy, which revealed a tumor on the posterior wall of the lower part of the stomach. Based on a biopsy, he was diagnosed with suspected adenocarcinoma, Group 4. In June 2017, he visited our hospital, and endoscopic submucosal dissection(ESD)was performed. The pathological diagnosis of the resected specimens was L, Less, 20×10 mm, Type 0-Ⅱc, tub1, pT1a(M), UL(-), ly(-), v(-), pHM0, pVM0, pStage ⅠA. He was referred to our department for the treatment of abdominal lymphadenopathy. His lymphadenopathy was localized in the gastric lesser curvature as an enlarged lymph node 15mm in size, based on the findings of contrast-enhanced CT. On FDG- PET/CT, we found a slight accumulation of SUVmax 2.4 in the early phase in the same lymph node. We could not confirm a diagnosis, and we performed laparoscopic dissection of the lymph node for diagnosis and treatment. The size of the specimen was 14×14mm, surface was smooth, and lymph node was elastic and soft. We found lymphoid follicles with atrophic germinal center using HE staining. We also found increased hyperplastic blood vessels around the germinal center, and he was diagnosed with hypervascular Castleman's disease.

[Long-Term Survival of a Patient with Para-Aortic Lymph Node Recurrence Who Underwent Lymph Node Dissection and Received Chemotherapy Following Curative Gastrectomy].

A 66-year-old man underwent total gastrectomy for gastric cancer. S-1 was administered as adjuvant chemotherapy. Abdominal CT showed para-aortic lymph node recurrence 31 months after the surgery. There was no other recurrence according to PET-CT, and we performed para-aortic lymph nodes dissection 41 months after the surgery. Lymph node recurrence in the retrocrural space was observed 37 months after the 2nd surgery. We administered S-1 plus L-OHP chemotherapy. After 4 courses, CT revealed that he had achieved complete response, and he has remained disease-free for 79 months after lymph node dissection. Some patients with para-aortic lymph node recurrence after curative gastrectomy may benefit from treatment including chemotherapy and surgical dissection.

Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial.

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.

[Two Cases of Pancreatectomy for Pancreatic Metastasis from Renal Cell Carcinoma].

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 Case of Long-Term Survival after Repeated Multidisciplinary Treatment for Liver Metastasis of Ampullary 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.

[A Case of Multiple Tumor Neurosurgery for Brain Metastasis of Colorectal Cancer].

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.

[A Case of Rectosigmoid Cancer with Intestinal Malrotation Treated with Laparoscopic Surgery].

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.

[Two Resected Cases of Non-Isolated Splenic Metastasis of Colon Cancer].

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.

[A Resected Case of Castleman's Disease That Was Difficult to Diagnose Preoperatively].

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.

[Pathological Complete Response in a Case of Advanced Esophageal Cancer with Widespread Lymph Node Metastases Treated Using Preoperative Chemotherapy with Docetaxel, Cisplatin, and 5-FU(DCF therapy)].

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.

[Two Cases of Systemic Steroid Therapy for Hyperbilirubinemia after Right Hepatic Lobectomy of Liver Metastasis from Colorectal Cancer].

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.

[Surgical Resection for Advanced Gastric Cancer with Portal Vein Tumor Embolus - Two Cases].

Gastric cancer with portal tumor embolus is rare and there is no definite strategy for its surgical resection. We report 2 cases ofgastric cancer with portal vein tumor embolus treated using gastrectomy and thrombectomy. Case 1: The patient was a 56- year-old man. We performed total gastrectomy, distal pancreatectomy, splenectomy, and thrombectomy. The patient was treated with 4 courses ofS -1 plus CDDP chemotherapy followed by S-1 administration. Eight months after surgery, CT revealed metastasis in the left adrenal gland and he died 2 years after surgery. Case 2: The patient was a 57-year-old man. We performed total gastrectomy, distal pancreatectomy, splenectomy, partial resection of the transverse colon, and thrombectomy. The patient was treated using adjuvant S-1 chemotherapy followed by UFT administration for 3 years. The patient has been alive with no tumor recurrence for the past 10 years. If there is no other therapeutic option for portal vein embolus, gastrectomy with thrombectomy could increase the possibility oflong -term survival.

Surgeons have knowledge gaps in the safe use of energy devices: a multicenter cross-sectional study.

BACKGROUND: Despite the widespread use of surgical energy devices and the potential for rare but serious complications, pilot data from North America suggest that surgeons and surgical trainees have knowledge gaps in their safe use. The purpose of this study was to determine baseline knowledge of general surgeons and surgical trainees regarding the safe use of electrosurgery (ES) across varying levels of experience in Japan. METHODS: Participants completed a 35-item multiple-choice question examination, testing critical knowledge of ES. The examination was developed according to the objectives and blueprints of SAGES' Fundamental Use of Surgical Energy™ curriculum. Sections of the examination included: "principles of ES," "ES-related adverse events," "monopolar and bipolar devices," and "pediatric considerations and interference with implantable devices." Scores were compared between PGY > 5 and PGY 1-5 participants. RESULTS: A total of 145 general surgeons and surgical trainees of all years after medical school (PGY 1-5: 57, PGY > 5: 88) from ten academic and five community hospitals completed the assessment (mean age 35; 91% male). The mean score in the entire cohort was 58 ± 12% (range 23-83%), with significantly higher scores in the PGY > 5 group compared to the PGY 1-5 group (60 ± 11 vs. 53 ± 12%, p < 0.01). Among all participants, 92% were not familiar with best practices when using ES on patients with a pacemaker; 44% believe that ES uses thermal energy from cautery; 19% did not know how to manage an operating room fire; 16% thought that a dispersive electrode should be cut to fit a child; and 27% believe that insulation failure in minimally invasive surgical instruments is mostly visible under careful inspection. CONCLUSIONS: General surgeons and trainees at all levels have knowledge gaps in the safe and effective use of energy devices, regardless of years of experience. There is a need for educational curricula to help address these gaps and contribute to safer surgery.

Predicting prolonged hospital stay after laparoscopic cholecystectomy.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: Thirteen factors closely related to hospital stay duration and LOS prediction score could predict the prolongation of a patient's hospital stay.

A case of retroperitoneal liposarcoma after delivery with expression of estrogen receptor: Report of a case.

INTRODUCTION: Liposarcoma is one of the most common soft tissue sarcomas; however, early diagnosis is rare as the tumor remains difficult and unpalpable for a prolonged period of time. PRESENTATION OF CASE: Here we report the first case of retroperitoneal liposarcoma associated with pregnancy and expression of estrogen receptor. A 34-year-old woman experienced persistent abdominal distension after her first delivery. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large (40cm×35cm), solid, palpable abdominal mass with fat attenuation displacing the ascending colon and the right kidney to the left. Laparotomy and an en-bloc resection of the tumor were performed; further, right nephrectomy and adrenalectomy were required. Histopathology showed a well-differentiated liposarcoma; approximately 10-20% of the tumor cells were ER-positive. DISCUSSION: Retroperitoneal liposarcoma associated with pregnancy is an extremely rare occurrence. Surgical resection is unquestionably the first choice of treatment, but complete resection is sometimes impossible due to the volume and depth of invasion of the tumor. In such cases, additional therapy for liposarcoma is important to improve prognosis. Thus, this report highlights the need for further research into hormone therapy. CONCLUSION: Retroperitoneal liposarcoma has a high local recurrence rate due to the difficulty in complete surgical resection; therefore, additional hormone therapy is important for improving the prognosis.

A phase II study of combined chemotherapy with 5-week cycles of S-1 and CPT-11 plus bevacizumab in patients with metastatic colon cancer.

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/m(2)) 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 <10%, other than diarrhea (10.9%). 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.