Search

Highlights • RFA and IVR treatment is expected to control local disease activity and improve survival rates for the liver metastasis from pNETs. • RFA and IVR treatment should be very carefully performed after pancreaticoduodenectomy or biliary reconstruction. • This report details our experience in using RFA combined with TAE to treat liver metastasis from a pNET after pancreaticoduodenectomy., Background Surgical resection is the first-choice treatment for operable liver metastases from pancreatic neuroendocrine tumors (pNETs). However, radiofrequency ablation, transcatheter arterial chemoembolization, and interventional radiology are expected to control local disease activity and improve survival rates in patients not eligible for surgery. Presentation of case A 54-year-old woman underwent pancreaticoduodenectomy for treatment of an 80-mm-diameter pancreatic head tumor. Histologically, the pancreatic tumor was diagnosed as a nonfunctional pNET (G2). At 38 months postoperatively, abdominal computed tomography showed two 15-mm-diameter liver tumors in segment 3 and segment 5/6, respectively. The patient requested nonsurgical treatment. Therefore, radiofrequency ablation combined with transcatheter arterial embolization was performed for the liver metastases. No complications occurred after the therapy. She was alive without recurrence at the time of this writing (33 months after the liver metastasis therapy, 74 months after the operation). Discussion Although interventional radiology and radiofrequency ablation should be very carefully performed after pancreaticoduodenectomy or biliary reconstruction, our patient showed a good response to treatment without serious complications. Conclusion This report details our experience in treating liver metastasis from a pNET after pancreaticoduodenectomy. The metastasis was successfully treated by radiofrequency ablation combined with transcatheter arterial embolization.

In our hospital, we measure the body composition of patients undergoing gastrointestinal surgery. For patients who have a skeletal muscle mass(SMM)of less than 90% of the ideal, we provide them with guidance on having oral nutritional supplements(ONS)and self-exercise therapy. Therefore, we perform operations after taking measures on preserving/improving patient's preoperative conditions. This study was aimed to evaluate the effects on body weight, SMM, and fat mass(FM)in the patients scheduled for gastrectomy.From January 2017 to December 2020, we retrospectively analyzed 64 gastric cancer patients whose body composition changes were measured at the time of initial diagnosis and immediately before surgery. The body composition was measured by a nutritionist using the BIA method, while the self-exercise therapy was instructed by a rehabilitation therapist.A total of 64 patients were divided into 2 groups: ONS group(36 patients)and Non-ONS group(28 patients). The median preoperative ONS administered to the ONS group was 15 packs. Body weight change showed a significant difference between the 2 groups(+0.73% and -0.91%[p0.01]in the ONS group and Non-ONS group respectively). SMM change showed no significant difference between the 2 groups(+1.18% and +0.64%[p=0.19]in the ONS group and Non-ONS group respectively). Likewise, FM change showed no significant difference between the 2 groups(-1.08% and -3.50%[p=0.39]in the ONS group and Non-ONS group respectively).This study suggested that SMM and FM could be preserved, and body weight could be increased by the support of preoperative ONS administration even in patients with gastric cancer close to having sarcopenia.

Highlights • The gallbladder of “pure” squamous cell carcinoma is a rare subtype of gallbladder cancer. • The advanced stage and infiltration of the gallbladder cancer into surrounding organ. • Radical resection for the advanced gallbladder carcinoma accompanied with general peritonitis is rare case., Introduction Squamous cell carcinoma (SCC) of the gallbladder is rare, accounting for merely 1–3% of all gallbladder cancers. Presentation of case A 59-year-old Japanese man was referred to our hospital with a chief complaint of right lower abdominal pain. He was diagnosed with gallbladder cancer after comprehensive testing. Computed tomography (CT) imaging revealed an enlarged gallbladder, and a lumen full of tumors (maximum tumor size was 90 mm in diameter.). The patient was, therefore, admitted to our department for the operation. After admission, the patient developed a fever and pain in his lower right abdomen. Palpation revealed masses in the abdomen and right hypochondrium. Blood tests revealed elevated levels of inflammatory markers. Therefore, a conservative treatment approach was performed prior to surgery. After then, the patient’s abdominal symptoms did not seem to worsen, and his vital signs were stable, leading us to continue the conservative treatment approach. The operation was conducted on a semi-urgent basis. Surgical findings: The patient was diagnosed with gallbladder cancer with traverse colon infiltration. We performed hepatic resection (S4a + S5), biliary reconstruction, lower (pyloric) gastrectomy, right hemicolectomy, and ileostomy. Histopathological findings revealed that the patient was diagnosed with advanced gallbladder SCC. Discussion Primary SCC of the gallbladder is associated with poor prognosis. Continuing to collect and document such cases will help to resolve this matter. Conclusion This report details our experience in treating a case of “pure” gallbladder SCC, a rare subtype of gallbladder cancer. Despite the complicating general peritonitis, we were still able to safely perform a radical resection to remove it.

Background/Aim: If both distant metastases and the primary tumour of colorectal cancer (CRC) are resectable, resection of the distant metastases is considered. The aim of this retrospective study was to determine the efficacy of curative resection of both primary and metastatic lesions in organs other than liver or lung in CRC patients. Patients and Methods: The medical records of 23 CRC patients who received R0 resection for primary and metastatic regions between 2009 and 2018 were retrospectively analyzed. Results: The 3-year overall survival (OS) in all 23 cases was 80.0%. There was no clinicopathological factor associated with OS on univariate analysis. Conclusion: Curative surgical resection appears to be useful for distant CRC metastases to organs other than liver or lung.

38 Background: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. Methods: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The schedule of 28-day oral administration followed by a 7-day rest period was repeated. Five 35-day cycles were repeated. The primary endpoint was 3-year disease-free survival. The secondary endpoints included 5-year overall survival and toxicity. Results: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The 5-year overall survival rates of group A and B were 89.7% and 91.0% (95% confidence interval, 83.3-92.8-84.8-93.8), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). Conclusions: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase. Clinical trial information: UMIN000005594.

A 71-year-old woman with advanced ascending colon cancer was admitted to our hospital. Abdominal computed tomography( CT)revealed locally advanced sigmoid colon cancer with suspected invasion of the liver and duodenum. The clinical stage of the disease was cT4bN3M1a, cStage Ⅳa, with wild-type RAS and UGT1A1 expression. An ileostomy was performed because of bowel obstruction. The patient received 6 courses of FOLFOXIRI plus bevacizumab(Bev). The only adverse event was Grade 3 neutropenia. Laparoscopic right hemicolectomy with lymph node dissection was performed. The pathological diagnosis was the absence of viable, Grade 3 carcinoma cells. This result suggested that preoperative FOLFOXIRI plus Bev chemotherapy is useful for the treatment of locally advanced colon cancer.

A 57-year-old man underwent curative resection for Stage Ⅰ sigmoid colon cancer; 6 years later, lung metastasis was detected and subsequently resected. Eight years after the first curative resection, retroperitoneal metastasis was detected and subsequently resected. Nine years after the first curative resection, a growing tumor was detected at the bottom of the right lower lobe of the lung. Partial lung resection was performed; pathological examination revealed a secondary tumor formed as a result of colon cancer metastasis. When we searched previous cases of late recurrence in colorectal cancer, the primary colorectal cancer was classified as StageⅠ or Ⅱ in more than half of the cases. Therefore, even after curative resection of Stage Ⅰ colon cancer, late recurrences may occur.

We report a case of advanced sigmoid colon cancer that was resected after chemoradiation therapy(CRT)following ineffective chemotherapy. A 59-year-old woman harbored a lower abdominal tumor the size of an infant's head and was diagnosed with a huge sigmoid colon cancer with invasion to the urinary bladder and metastases to the para-aortic lymph nodes. The patient received 2 courses of modified FOLFOX6(mFOLFOX6)plus cetuximab therapy, which was assessed as ineffective; She then received CRTwith 50.4 Gy in 28 fractions plus concurrent oral S-1(100mg/day for 28 days). Tumor shrinkage in the primary lesion was achieved after CRT; total pelvic exenteration with the removal of metastatic para-aortic lymph nodes was then performed 5 months after the first diagnosis. This case of locally distant advanced colon cancer in the pelvic cavity coexisting with resectable metastatic lesions suggested that CRTmight contribute to successful local treatment after the failure of preoperative chemotherapy.

An 81-year-old woman underwent preoperative chemoradiotherapy(CRT)for advanced lower rectal cancer with vaginal invasion. However, she refused surgery and received additional radiotherapy. We detected a rectal-vaginal leak, so we performed ileostomy with double orifices and chemotherapy. As the tumor and vaginal leak increased, we performed laparoscopy- assisted abdominoperineal resection and vaginal posterior wall resection after 16 months of CRT. Although adhesion occurred due to inflammation and tumor invasion after the CRT, surgery could be performed safely. Despite the advanced age of the patient, complications did not occur, and no recurrence was observed for 66 month after the surgery. In rectal cancer, operation is usually performed until 6 to 8 weeks after CRT, but in our case, the surgery was performed after a long interval, with good results. Thus, we report the case herein.

A 63-year-old man was followed-up for diabetes mellitus. During follow-up, computed tomography(CT)showed dilatation of the main pancreatic duct in the tail of the pancreas. Abdominal enhanced CT revealed a 25 mm tumor in the body of the pancreas. Endoscopic ultrasound-fine needle aspiration(EUS-FNA)was performed, and the pathological diagnosis was adenocarcinoma. Therefore, based on the diagnosis of pancreatic body carcinoma, distal pancreatectomy with splenectomy was performed. The postoperative course was uneventful. Histological and immunohistochemical examination revealed that the tumor consisted of a ductal carcinoma and a neuroendocrine component. Therefore, combined pancreatic tumor (fT3N1M0, StageⅡB)was diagnosed. The patient subsequently received postoperative adjuvant chemotherapy(S-1 100mg/ day), and survived without recurrence 6 months after the operation. We report this case of combined pancreatic tumors with a review of the literature.

A 70-year-old man was referred because of suspected gallbladder cancer and gallstones. Contrast-enhanced CT, EOB-MRI and PET-CT could not completely rule out gallbladder cancer. The patient preferred follow-up without surgery. At 4 months after initial examination, the gallbladder wall thickening showed improvement, but appeared worse at 9 months after initial examination. Therefore, we decided to perform surgery. Since malignant findings were not observed on rapid intraoperative pathology, we performed a cholecystectomy and right hemicolectomy because of inflammation in the transverse colon. Pathological examination diagnosed xanthogranulomatous cholecystitis. The imaging appearance of xanthogranulomatous cholecystitis varies, and also changes over time, making it difficult to distinguish from advanced gallbladder cancer. We experienced a case of xanthogranulomatous cholecystitis that changed over time, and report this case with a review of the literature.

A 60-year-old man was admitted for a liver mass(S3), which rapidly increased in size during intraductal papillary mucinous neoplasm(IPMN)follow-up. Although EOB-MRIwas performed, the mass could not be accurately diagnosed as hepatic cancer. Thus, we performed a lateral segmentectomy. In the resected specimen, a solid tumor mass was clearly bound in segment 3 of the liver. Since histopathology revealed no malignant cells and many IgG4-positive cells, we confirmed the diagnosis as IgG4-related inflammatory pseudotumor of the liver. IgG4-related diseases occur in various organs in the body, and they are known to associate with autoimmune pancreatitis and sclerosing cholangitis, but an IgG4-related inflammatory pseudotumor of the liver is a rare disease. It is often difficult to distinguish from hepatic cancer and surgical resection is performed.

We report a case of advanced sigmoid colon cancer resected via laparoscopic surgery after preoperative chemotherapy. A- 55-year-old man visited our hospital with diarrhea. CTrevealed a giant tumor in the sigmoid colon, and surrounding lymph node enlargement was also noted. The tumor appeared to be locally advanced; thus, preoperative chemotherapy was started. Due to the possibility of obstruction, we constructed an ileostomy laparoscopically. The tumor was found to be RAS wild, and 4 courses of mFOLFOX6 plus panitumumab were given. Follow-up CTshowed remarkable tumor reduction allowing laparoscopic resection; as such, laparoscopic sigmoidectomy was performed successfully. Chemotherapy with molecular-targeted drugs is a promising method to make laparoscopic surgery possible for advanced colorectal cancer.

To elucidate ideal strategy of treatment for advanced lower rectal cancer, we investigated 11 patients with clinically suspected lateral pelvic node(LPN)metastasis among 36 patients who received neoadjuvant chemoradiation therapy(NCRT). Nodal metastasis was diagnosed as positive when the major axis of a lymph node was over 7mm in computed tomography(CT). Both tumor and nodal downstaging were observed in CT after NCRT; pathological complete response and ypN0 was obtained in 2(18.2%)and 6(54.5%)cases, respectively, and positive LPN was observed only in 2 cases. All of 4 cases who were diagnosed as ycN0 in CT after chemoradiation were confirmed as ypN0. Extended examination with 36 patients who underwent NCRT showed that 85% of 21 ycN0-cases were confirmed to be ypN0. As a conclusion, NCRT for lower rectal cancer with suspected LPN metastasis was highly effective, and omitting lateral node dissection when all nodes turned to be less than 7mm on CT, can be a hopeful option.

The patient was a 79-year-old woman, who had undergone pancreaticoduodenectomy(PD)for lower bile duct carcinoma in our hospital(pT3N0H0P0M0, fStage III ). Four years 6 months after the initial operation, abdominal CT revealed left bile duct expansion and hilar bile duct thickening. Therefore, based on the diagnosis of perihilar cholangiocarcinoma originating from the left hilar duct, we performed left lobectomy with caudate lobectomy and biliary tract reconstruction. The surgical specimen showed a tumor in the left hilar bile duct. Histopathological diagnosis of the tumor was a moderately differentiated adenocarcinoma(pT2aN0H0P0M0, fStage II ). Surgical margins were histologically negative. Since the tumor was located away from the anastomosed site of the cholangiojejunostomy, we determined that the tumor was not a recurrence but a metachronous cholangiocarcinoma. The postoperative course was uneventful. The patient survived without recurrence 2 years after the second operation. The possibility of heterochronic biliary carcinomas should be considered during follow-up evaluation. We report this case of metachronous cholangiocarcinoma that occurred 4 years 6 months after PD, with a review of the literature.

Some patients with unresectable colorectal cancer can be treated by chemotherapy leaving the primary tumor unresected, but indications and implications of a later resection of the primary tumor (RPT) are often controversial. We investigated 5 patients whose primary tumors were resected during chemotherapy, either panitumumab or bevacizumab. The median age of these patients was 63 years and all were men. The unresectable disease was liver metastases in 4 patients and a primary tumor in 2 patients. A diverting stoma was constructed before initiation of chemotherapy in 2 patients. The median interval until RPT was 8.3 months and the reasons for resection were the appearance of obstructive symptoms in 3 patients and a desire for stoma closure in 2 patients. The size of the primary tumor had decreased until RPT in all patients. RPT was performed successfully in all patients, but 2 of the 3 operations that were initiated laparoscopically had to be converted to open surgery. Intensive chemotherapy was resumed in all patients and median survival after RPT was 19 months, including a patient whose liver metastasis was also resected later. RPT can relieve obstructive symptoms and close stomas. Because intensive chemotherapy is still possible and a lengthy survival can be expected after RPT, it should be considered not merely as a palliative option but also as a treatment strategy.

We report a case of a 62-year-old woman with a growing liver tumor that was difficult to differentiate from hepatocellular carcinoma (HCC). Abdominal CT revealed a hypervascular tumor (36 mm in diameter) in segment 3 of the liver that showed early enhancement and which had grown from 30 mm to 36 mm over the previous year. A fatty liver and gallstones were also detected. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor on both T1- and T2-weighted images, and EOB-MRI revealed a mass that showed high signal intensity in the hepatobiliary phase. The imaging findings were not typical for HCC; however, the possibility of malignancy could not be ruled out due to the enlargement of the mass. Therefore, in February 2015, we performed a laparoscopic left lateral segmentectomy with cholecystectomy. After a good postoperative course, the patient was discharged from the hospital 11 days after surgery. Histological assessment revealed the tumor was focal nodular hyperplasia (FNH).

症例は40歳代の男性で，25歳頃より腸閉塞の診断で入退院を繰り返し，保存的療法で改善していた．2008年6月にS状結腸過長症と診断され，他院で腹腔鏡下S状結腸切除術を施行された．しかし同年7月に再び腸閉塞症状のため当院に入院した．入院3日目に腹膜炎症状が出現し，緊急手術を施行した．上行結腸が捻転しており同部位より口側結腸が拡張していたため，結腸右半切除術を施行した．術後も腸閉塞状態が改善せず，腹部膨満症状を改善するため，回腸人工肛門造設を施行した．その後，慢性偽性大腸閉塞症を考え，同年12月に結腸全摘術を施行した．症状の改善は認めたが，術後も腹部単純X線検査で小腸は著明に拡張した状態であったため，慢性偽性小腸閉塞症と最終診断した．術後1年経過した現在，蠕動促進薬を内服して日常生活を送っている状態である．

Background Portal or splenic vein thrombosis (PSVT) is a common disorder after laparoscopic splenectomy (LS). Splenomegaly is a well-known risk factor for PSVT. However, no treatment strategy for PSVT has been established. Methods Thirty-three consecutive patients who had undergone LS and postoperative imaging surveillance were examined. PSVT was classified according to the site of thrombosis. We evaluated patient background, operative factors, and clinical symptoms. Results Spleen weight of patients with PSVT (n = 17, median 218 g) was greater than that of patients without PSVT (n = 16, median 101 g). Seven patients developed thrombosis involving the entire splenic vein (total splenic vein thrombosis), and 4 of them had clinical symptoms (fever >38°C and/or abdominal pain). The incidence of clinical symptoms was significantly more frequent in patients with than without total SVT. Operation time, blood loss, and spleen weight were also significantly greater in patients with total SVT. Multiple logistic regression analysis demonstrated spleen weight was the strongest predictor of PSVT and total SVT. Conclusion Patients with total SVT have greater risk factors for PSVT and frequently have clinical symptoms. They are candidates for anticoagulation therapy.

A 67-year-old-man came to our hospital for further evaluation of a liver tumor detected by abdominal ultrasonography at another hospital. Abdominal computed tomography showed a tumor (8 cm in diameter)in the left lobe of the liver, with invasion of the left and middle hepatic veins, and multiple lymph node metastases. Liver biopsy examination revealed intrahepatic cholangiocellular carcinoma (cStage IVB). Therefore, chemotherapy with gemcitabine(GEM)was administered. The hepatic tumor and multiple lymph nodes were reduced in size after eight courses of GEM chemotherapy. In May 2013, we performed an extended left hepatectomy with biliary tract reconstruction and extended lymph node dissection. The histological diagnosis was intrahepatic cholangiocellular carcinoma, pT3N0H0P0M (-), fStage III. The patient's postoperative recovery was good, and 1 month after surgery, the patient received 6 course of postoperative adjuvant GEM chemotherapy. No serious adverse events occurred during the postoperative adjuvant therapy period. The patient is alive without recurrence 14 months after surgery and 23 months after diagnosis.

A 64-year-old man presented with a chief complaint of abdominal pain. An abdominal computed tomography (CT) scan showed a mass 30-mm in diameter at the splenic flexure, and we diagnosed a retroperitoneal abscess. Conservative therapy was successful, and the patient was discharged. However, 1 month later, he again experienced abdominal pain. To reassess the abscess, contrast-enhanced abdominal CT was performed. In addition to the retroperitoneal abscess, the CT scan showed an approximate 30-mm mass in the head of the pancreas with no contrast uptake. The abscess was also detected by endoscopic retrograde pancreatography. We suspected but could not confirm pancreatic cancer. Two months later, the patient developed obstructive jaundice. At this time, we diagnosed pancreatic cancer, and subtotal stomach-preserving pancreaticoduodenectomy was performed. The histopathologic diagnosis was pancreatic cancer, T4, N0, M0, Stage IVa. The postoperative course was favorable, and the patient received postoperative adjuvant chemotherapy. He remains alive without recurrence 15 months after surgery.

Massive lymph node metastasis of the para-aortic region and supraclavicular lymph nodes, Virchow's lymph node metastasis due to colon cancer, is extremely rare. We herein report a case of such systemic lymph node metastasis that was successfully treated with a combination of irinotecan (CPT-11) and UFT, a combination drug of tegafur and uracil. The patient was a 57-year-old woman who had a tumor in the ascending colon, and massively swollen para-aortic and supraclavicular lymph node metastasis. She was treated with combination chemotherapy of CPT-11 and UFT. The main tumor was detected as a decompressed scar, and the supraclavicular and para-aortic lymph nodes had completely disappeared after the second cycle of treatment. A histopathological examination and immunohistochemistry with cytokeratin showed complete remission of adenocarcinoma in the tumor and para-aortic lymph nodes. She remains alive without recurrence 52 months after chemotherapy. Combination chemotherapy of CPT-11 and UFT may be of potential value in the treatment of advanced colorectal carcinoma, and both histopathological and immunohistochemical confirmation of a complete remission may indicate prolonged disease-free survival.

A 66-year-old woman was diagnosed with pancreatic tail cancer, and she was referred to our hospital. Abdominal computed tomography(CT)revealed a tumor(2.5 cm in diameter)in the pancreatic tail, with invasion to the spleen and splenic vein. In February 2013, we performed distal pancreatectomy with splenectomy, left adrenal gland resection, and D2 lymph node dissection. Diagnostic peritoneal lavage cytology during surgery was positive; however, we performed curative resection because there were no signs of peritoneal dissemination and distant metastasis. The patient was discharged from the hospital 23 days after the operation, with good postoperative course. Histological diagnosis was pancreatic tail cancer, pT4N0H0P0M(-) fStage IVa. Subsequently, the patient received postoperative adjuvant chemotherapy(TS-1: 100mg/day, 4 courses)combined with Wilms'tumor 1(WT1)peptide-pulsed dendritic cell therapy. No serious adverse events occurred during the postoperative adjuvant therapy. The patient remains alive without recurrence 16 months after the operation.

Clinical studies have shown that oxaliplatin, a novel platinum derivative, is a potent chemotherapeutic agent for colorectal cancer when combined with 5-fluorouracil and leucovorin. Although the toxic activity is based on covalent adducts between platinum and DNA, its actual biological behavior is mostly unknown. In an effort to explore the mechanism of tumor susceptibility to oxaliplatin, we examined the cytotoxic effects of oxaliplatin in colorectal cancer cell lines in reference to p53 gene status. Although p53 gene status did not clearly predict sensitivity to oxaliplatin, p53 wild-type cells including HCT116 were sensitive but HCT116 p53−/− were found to be resistant to oxaliplatin. Oxaliplatin caused strong p21waf1/cip1 induction and G0-G1 arrest in p53 wild-type cells, whereas cisplatin did not induce G0-G1 arrest. Assays using p53 wild but p21waf1/cip1 null HCT116 cells revealed that oxaliplatin did not show G0-G1 arrest and reduced growth-inhibitory effects, suggesting that p21waf1/cip1 may be a key element in oxaliplatin-treated p53 wild-type cells. Although HCT116 is DNA mismatch repair–deficient, a mismatch repair–proficient HCT116+ch3 cell line displayed similar responses with regard to p21waf1/cip1-mediated growth inhibition and G0-G1 arrest. In p53 mutant cells, on the other hand, oxaliplatin caused an abrupt transition from G1 to S phase and eventually resulted in G2-M arrest. This abrupt entry into S phase was associated with loss of the p21waf1/cip1 protein via proteasome-mediated degradation. These findings suggest that p21waf1/cip1 plays a role in oxaliplatin-mediated cell cycle and growth control in p53-dependent and -independent pathways.

Clinical studies have demonstrated that oxaliplatin, a novel platinum derivative, is a potent chemotherapeutic agent, especially when combined with other reagents. The aim of the present study was to explore the mechanism of such action.Using colon cancer cell lines, we examined changes in cell cycle, apoptosis and mitotic catastrophe induced by oxaliplatin and/or paclitaxel.Oxaliplatin at its IC(50) induced apoptosis and cell cycle arrest at G(2)-M phase. Western blot analyses indicated that oxaliplatin decreased mitosis-commencing protein cdc2 and anti-apoptotic proteins, phospho-Bcl(2) and Bcl-xl in the three colon cancer cells tested. Since cdc2 stabilizes survivin, a putative IAP (inhibitor of apoptosis) family member, through phosphorylation of Thr34, we examined the level of survivin and found a marked decrease due to oxaliplatin. This finding is of particular interest because survivin is a promising molecular target against various human cancers and a key molecule involved in both apoptosis and mitotic catastrophe. When used in combination with paclitaxel (taxol), a putative apoptosis-inducing reagent, the isobologram indicated that the taxol-oxaliplatin sequence or taxol plus oxaliplatin had synergic or additive effects, while the oxaliplatin-taxol sequence resulted in a prominent antagonism. The taxol-oxaliplatin sequence caused marked growth inhibition of DLD1 and SW480 cells, possibly due to upregulation of apoptotic and non-apoptotic pathways, respectively. Morphological surveys indicated that the non-apoptotic process could be mitotic catastrophe.Our results suggest that oxaliplatin that potently inhibited survivin may exert outstanding cytotoxic effects when combined with certain chemoreagents through enhancement of apoptosis and mitotic catastrophe.

発症早期に診断し超音波ガイド下に整復,待機的手術を行った閉鎖孔ヘルニアの1例を経験した.症例は40歳,女性で左鼠径部痛を主訴に来院, CTで左恥骨筋と外閉鎖筋の間に円形腫瘤を認め閉鎖孔ヘルニアと診断した.超音波プローべを用い嵌頓腸管を整復した後,待機的に鼠径法で根治手術を施行した. 閉鎖孔ヘルニアの報告は多数みられるが,本症例は若年である点と明らかなヘルニア嚢が認められない初期段階での発症である点が特徴的であった.近年ではCTを中心とした画像診断の進歩によりほとんどの例で術前診断がなされている.手術は依然として緊急開腹術が多いが,発症早期に嵌頓腸管の解除が得られればより侵襲が少ないアプローチでの待機的手術も考慮される.

A 36-year-old woman with benign phyllodes tumor of the left breast had undergone lumpectomy 1 year ago and was admitted to our hospital because of a left breast mass on the operation scar. Ultrasonography showed a 35 mm low-echoic, elliptical mass with a high depth to width( D/W) ratio in the C area and a 10 mm low-echoic, polygonal mass with a high D/W ratio in the E area. Histological examination of an ultrasonography-guided vacuum-assisted biopsy specimen indicated recurrent phyllodes tumor. Since both tumors were assumed to be recurrent phyllodes tumors, quadrantectomy was performed. Finally, the mass in the C area was diagnosed as a recurrent phyllodes tumor and the mass in the E area was diagnosed as a fibroadenoma. A non-invasive ductal carcinoma was incidentally detected between the 2 tumors, and the surgical margin was negative. Radiotherapy was performed on the remnant breast tissue.

We treated 9 patients diagnosed with brain metastasis from breast cancer. Although 1 patient was initially diagnosed as having Stage IV disease, 5 had Stage I/II early breast cancer. All patients had defined brain metastasis after chemotherapy. Brain metastasis was symptomatic in 7 patients, 4 of whom had brain edema, and asymptomatic in 2 patients. The median survival time from breast cancer metastasis was 23 days for patients who did not receive radiotherapy and 19.6 months for those who received radiotherapy. Among the patients treated with radiotherapy, the median survival time was 4.3 months for patients who did not receive further treatment and 19.7 months for those who received chemotherapy or chemotherapy with trastuzumab. One patient with a solitary brain metastasis underwent stereotactic radiosurgery, and treatment is being continued for 1 of the 2 patients who received systemic therapy after whole-brain radiotherapy and additional stereotactic radiosurgery at recurrence to control brain disease. Systemic treatment after radiotherapy is important for brain metastasis from breast cancer, and early diagnosis of brain metastasis facilitates the use of various available treatments.

Twenty patients( 30 nodules) with metastatic liver cancer( MLC) and 10 cases with hepatocellular carcinoma( HCC) treated by stereotactic radiotherapy (SRT) were analyzed. SRT was administered at 48.0 or 52.8 Gy/4 Fr/1 wk. The response rate (RR) in MLC patients was 78%, and 11 patients survived longer than 1 year and 9 patients survived as long as 2 years. Clinical analysis suggests that the ideal indications for SRT in MLC are solitary nodules in patients without extrahepatic disease who have undergone systemic chemotherapy. Although RR of SRT for HCC was as high as 85%, intrahepatic recurrence was observed in all patients and 6 patients died within 1 year. Further analysis is needed to determine the indication for SRT in HCC patients.

Chemoradiotherapy followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer. Although this approach decreases the risk of local recurrence, pelvic radiation is associated with long-term morbidity and delays systemic treatment. We conducted this study to evaluate the feasibility of neoadjuvant capecitabine and oxaliplatin (XELOX) plus bevacizumab as a treatment for high-risk localized rectal cancer.Patients with T4 or lymph node-positive rectal cancer were treated with three cycles of XELOX plus bevacizumab and one additional cycle of XELOX. This was followed by TME performed 3-8 weeks after the last chemotherapy session.Twenty-five patients were recruited between December 2009 and November 2011. In seven of the patients (28.0 %), grade 3-4 adverse events occurred. After preoperative chemotherapy, the frequency of tumor (T) downstaging was 69.6 %, and that of lymph node (N) downstaging was 78.9 %. Seven patients discontinued the treatment after 2-3 cycles of XELOX plus bevacizumab. The frequency of subsequent surgery was 92 %, and all patients underwent R0 resections. Postoperative complications occurred in six patients (26.1 %). One patient achieved a pathological complete response (pCR) for the primary tumor and lymph nodes, whereas an additional four patients achieved near-pCR. After a median follow-up of 31 months, five patients displayed metastatic progression, including one who suffered local recurrence.XELOX plus bevacizumab followed by TME is feasible for high-risk localized rectal cancer, as it achieves good tumor regression and causes manageable toxicity.

A 59-year-old woman was admitted to our hospital because of right chest pain. CT scan showed a mass on the right abdominal wall and bilateral pleural effusion. The histological diagnosis following core needle biopsy was undifferentiated sarcoma. The right pleural effusion gradually increased despite negative cytology. Although we planned chemotherapy for the clinically diagnosed pleural invasion, thrombocytopenia as a paraneoplastic syndrome appeared. The minimum thrombocyte count was 4,000/mm3. While transfusion was not effective, per os dexamethasone at 2.0 mg/day kept the thrombocyte count at around 6×10 4/mm3. Anti-thrombocyte antibody was negative. Tumor resection surgery with partial diaphragm resection and 11th and 12th rib resection, and abdominal wall plasty with mesh was performed. The final histological diagnosis was dedifferentiated liposarcoma. The thrombocyte count returned to the normal range just after the operation. However, she died of pleural dissemination, peritoneal dissemination, and local recurrence 69 days after the operation.

CASE 1: A 64-year-old woman with right breast cancer had a partial mastectomy and radiotherapy four years ago was admitted to our hospital because of right breast mass. The vacuum associated biopsy of tumor resulted in breast sarcoma, thus a nipple-spearing mastectomy was performed. The final histological diagnosis was stromal sarcoma, and was identical to histological findings of malignant fibrous histiocytoma. Three months after the operation, a chest wall recurrence appeared. Although tumor resection with latissimus dorsi flap was performed, there were pleural dissemination and malignant pleural effusion. She died six months after the first surgery. CASE 2: A 60-year-old woman was admitted to our hospital because of left breast mass, but she refused a further clinical examination. She readmitted fourteen months later due to a huge sized left breast mass with necrosis and smelling discharge. CT scan showed a huge tumor of left breast and multiple lung metastases. Biopsy of the tumor resulted in breast sarcoma. Total mastectomy with split thickness skin grafting was performed. The final histological diagnosis was identical to the first case. A local recurrence appeared thirty days after the operation, and she died fifty-one days after the operation.

We investigated 13 cases of axillary-lymph-node recurrence, who received an operation for an early stage breast cancer. They are the first recurrence of only regional without metastatic disease; the 4 patients, who had sentinel-lymph-node by biopsy at first operation, received an axillary lymph adenectomy, and 5 patients received re-lymph-adectomy after axillary lymph node dissection. The other 4 patients received only systemic therapy. Receptor conversion between primary and lymph-node recurrent site was identified for ER in 2 patients; one showed a lower expression of ER and the other showed for HER2. These led to a change in the subsequent treatment plan; 6 patients had systemic chemotherapy after recurrence, 1 patient had endocrine, 2 patients had trastuzumab and 4 patients continued the same treatment prior to surgery. Ten out of 13 patients were alive without recurrence, and 3 patients were with distant metastasis. However, one of the 3 patients who had a distant metastasis died due to brain and lung metastasis. Axillary node recurrence should be treated with axillary dissection, if possible, and receptor measurement in primary and recurrent site is useful for subsequent treatment.

Esohophageal stents are often used in treating malignant stricture. But, when stents are placed across the esophagogastric junction, they may lead to esophagogastric reflux. We report a case of successfully treated esophagogastric strictures using the new stent with anti-reflux mechanism (long cover type Niti-S™ esophageal stent). A 78-year-old man presenting with severe strictures from the lower esophagus to cardiac part of stomach was histopathologically diagnosed as adenocarcinoma. CT scan images showed multiple liver metastatic tumors. However, he refused chemotherapy. Palliation using long cover type Niti-S™ esophageal stent was performed. No adverse effect was occurred. He started solid meals on the 7th postoperative day. He was thereafter able to ingest solid meals without the symptom of esophgogastric reflux and stenosis until he died of the primary disease two month later.

We reported three cases of patient with triple negative skin metastasis after mastectomy of breast cancer. All three cases had received radiotherapy for skin metastasis. Radiation therapy was effective for recurrent sites, and could improve patient's QOL. After radiotherapy, 2 patients died due to a distant metastasis. Case 1 was resistant to chemotherapy. Case 2 was no indication of chemotherapy because of dementia metastases. Case 3 was the only one continued chemotherapy. It appears that a further consideration was needed for the timing of radiotherapy to be performed among the treatments of locoregional recurrence and distant metastasis of breast cancer.

We report two cases of bronchiolitis obliterans organizing pneumonia (BOOP) induced radiotherapy after surgery of breast cancer. One of the patients was a 58-year-old woman. She underwent a conserving surgery for bilateral breast cancers, and received radiation therapy to the remaining part of bilateral breasts. Two months after the termination of irradiation, cough, fever and general fatigue developed. We clinically diagnosed this case as BOOP after radiation therapy. After initiation of oral steroid therapy, the clinical symptoms and radiographic findings disappeared. Another patient was a 57-year-old woman. She underwent radical mastectomy for right breast cancer. A month after the operation, she suffered from local recurrence, so radiation therapy to the thoracic wall was performed. After irradiation, resection of the thoracic wall lesion was performed because of malignancy from local skin biopsy specimen. Two months after the termination of irradiation, cough, dyspnea and fever developed. We clinically diagnosed this case as radiation-induced BOOP by BAL and TBLB findings. After an initiation of steroid therapy, the clinical symptoms and radiographic findings disappeared. It is important to be aware of BOOP as a complication in the patient who was given radiation after surgery of breast cancer.

A 60-year-old female who was diagnosed as gastric cancer underwent distal gastrectomy and received adjuvant chemotherapy (S-1 therapy). After 6 months, the tumor marker (CEA) was elevated. CT revealed para-aortic lymph nodes enlargement. Lymph node metastasis was confirmed. The patient was administered combination chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP) Seven months later, CT revealed lymph node metastasis had disappeared. After judgment of complete response (CR), we continued the treatment for 22 months. The patient was followed without any recurrence in May 2010.

We evaluated a surgical resection and chemo-endocrine therapy and prognosis for patients with local recurrence or axillary lymph node metastasis of breast cancer. Twenty-one patients with local recurrence or axillary lymph node metastasis without a distant metastasis were enrolled in this study. Thirteen of the 21 patients underwent a surgical resection. Resection of recurrent lesion in residual breast after breast conserving therapy for six of the 13 patients, axillary lymph node dissection (ALND) for four, and resection of thoracic wall lesion for three were performed. Five of the patients who underwent resection of residual breast lesion, four of the patients who underwent ALND and two of the patients who underwent resection of thoracic wall lesion have survived. One of the patients who underwent resection of residual breast lesion and one of the patients who underwent resection of thoracic wall lesion were dead. In eight non-operable patients, five were dead and three have survived. Median recurrence free interval was 24 months in operable patients and 27 months in non-operable patients. Median survival time after recurrence was 29 months in operable patients and 12 months in non-operable patients. The surgical with chemo-endocrine therapy promises to control well to local recurrence or axillary lymph node metastasis for the patients we selected.

The platinum-based chemotherapeutic agent oxaliplatin displays a wide range of antitumor activities. However, the underlying molecular responses to oxaliplatin in esophageal cancer remain largely unknown. In the present study, we investigated the effect of oxaliplatin on two esophageal cancer cell lines, squamous cell carcinoma (TE3) and adenocarcinoma (TE7). Following cell-cycle arrest at G(2) phase after oxaliplatin treatment, TE3 cells died via apoptosis and TE7 cells died via mitotic catastrophe. Survivin was inhibited more in TE7 cells compared with TE3 cells, but inhibition of survivin using small interfering RNA induced mitotic catastrophe in both cell lines. Further investigations indicated that survivin promoter activity was also inhibited by oxaliplatin. Among mitotic catastrophe-associated proteins, 14-3-3 sigma was decreased in TE7 cells; no evident changes were observed for aurora kinases. Oxaliplatin-induced apoptosis in the TE3 cells was caspase dependent. However, downregulation of Bad, Bid, Puma, and Noxa, lack of cytochrome c release, and limited loss of mitochondrial membrane potential in early phase indicated possible initiation by pathways other than the mitochondrial pathway. Mechanistic studies showed that downregulation of survivin by oxaliplatin in TE7 cells was partially due to the proteasome-mediated protein degradation pathway and partially due to the downregulation of Sp1 transcription factor. Similar results were obtained for another gastric adenocarcinoma cell line, MKN45, in which survivin was previously shown to be inhibited by oxaliplatin. These data indicate that survivin may be a key target for oxaliplatin. The ability of oxaliplatin to induce different modes of cell death may contribute to its efficacy in esophageal cancer.

We report two patients having recurrent breast cancer with brain metastases that was controlled well with a gamma knife radio-surgery. The patient is a 50-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy, and extended right lobectomy of the liver were performed in December 2001. Afterward, pleurodesis was carried out to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study revealed brain metastases with a diameter of 1 cm in her right midbrain in April 2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was started, and she took the regimen continuously. Another patient is a 56-year-old woman. She underwent skin sparing mastectomy with axillary lymph node dissection for right breast cancer in November 2002. Metastases to the base of her skull were found in October 2004, so a gamma knife radio-surgery was carried out. After the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In both of the two patients, the metastatic brain tumors have not shown growth so far and are under good control as of March 2006.

It is known that p16 INK4 tumor suppressor gene expression in colon cancer cells is repressed by methylation at the CpG island of promoter, but in vivo silencing of p16 gene is not fully understood. Some studies showed that primary colorectal cancer (CRC) tissues often overexpress the p16 protein, while others showed the high incidence of p16 methylation. The aim of this study was to clarify p16 gene regulation in vivo. We used real-time methylation- specific PCR (MSP) to examine density of p16 methylation, and immunohistochemistry, Western blot analysis to determine p16 protein expression. Methylation was detected in 5 CRC cell lines tested and 9 of 21 (42.9%) CRCs. Four of 5 CRC cell lines did not express p16 mRNA, but 6 of 9 CRCs did express p16 mRNA even with methylation. Real-time MSP showed that CRC tissues had a wide variety in methylation density (methylation index: 0.28-0.91) and that highly methylated CRC tissues displayed significantly lower p16 mRNA expression than those with no-methylation or low- methylation. Immunohistochemistry showed that the majority of CRCs (53 of 55: 96.4%) overexpressed the p16 protein. Low p16 expression was associated with lymph node meta- stasis (p=0.003) and large tumor size (p=0.048). Western blot in a subset of non-tumor and tumor samples showed a consistent overexpression of the p16 protein. These results showed that CRC tissues displayed variable methylation density, which may be characteristics of p16 gene methylation in vivo. Our data suggest that a low p16 expression due to methylation may contribute to tumor enlargement and expansion of CRC.

We previously reported in a retrospective study that CEA-based RT-PCR was useful for predicting the prognosis of patients with node-negative colorectal cancer. RT-PCR is well established for laboratory use, but many issues remain to be resolved prior to its clinical application. In addition to the false positive rate of RT-PCR, we addressed several issues, including the timing of lymph node sampling, stability of RNA after surgery, and reproducibility of results. After appropriate modification, including development of a tissue sampling kit, a multi-institutional clinical study was commenced prospectively from November 2001, and 100 patients were enrolled for examination of micrometastasis. RNA was stable in lymph nodes for up to 3 h after surgical resection. This range of sampling time was acceptable to the surgeons. RNA was well preserved in RNA later at -20 degrees C for 3 weeks. Dilutions of MKN45 and LoVo cells served as positive controls for conventional PCR since these controls were found to be highly stable and ensured reproducibility. Moreover, simultaneous use of quantitative PCR (Light Cycler) ensured double confirmation of the results. Our clinical study showed that the quality of RNA was excellent or good in most samples (98 of 100; 98%). Twenty-four of 98 (24.5%) cases were judged to be micrometastasis-positive. In conclusion, the current translational research study established a clinically feasible RT-PCR system for micrometastasis. Our system could potentially be useful as a clinical tool.