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Preoperative systemic inflammation has been reported to predict survival in patients with various cancer types. In patients with colorectal liver metastasis (CRLM), the prognosis is poor despite therapeutic advances in the field. Here, we aimed to evaluate the prognostic role of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR) in patients with CRLM after hepatic resection.This retrospective study included 104 patients who underwent hepatic resection for CRLM between October 2010 and 2021 at the National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan. The association between clinicopathological variables, including various inflammatory biomarkers [LCR, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), CRP-to-albumin ratio (CAR), and prognostic nutritional index (PNI)], and overall survival of the patients was investigated using univariate and multivariate analyses.The optimal cut-off values for each biomarker by receiver-operating characteristic analysis were as follows: LCR: 12,720; PLR: 150; NLR: 4; CAR: 0.023; and PNI: 44.8. The 1-, 3-, and 5-year overall survival rates were 97.0%, 71.3%, and 56.8%, respectively. On univariate analysis, LCR12, 720, PLR0.14, body mass index24 kg/mLCR may be an independent prognostic predictor in patients after hepatic resection for CRLM. Therefore, the assessment of LCR as a biomarker may help in treatment planning.

Difficult laparoscopic cholecystectomy (DLC) may increase the risk of complications and extend the duration of hospitalization. The aims of this study were to evaluate the predictive value of C-reactive protein/albumin ratio (CAR) for DLC in patients with acute cholecystitis (AC) diagnosed according to the Tokyo Guidelines 2018 and to develop a preoperative predictive model for DLC.We retrospectively analyzed 205 patients who had laparoscopic cholecystectomy for AC between January 2012 and December 2020. We defined DLC cases as having one of the following factors: blood loss ≥50 mL, operative time ≥150 minutes, or conversion to open surgery. We classified the remaining cases into the non-DLC group.Overall, 127 (62.0%) and 78 (38.0%) patients were grouped into the DLC and non-DLC groups, respectively. Patients in the DLC group had: higher severity grade, which was assessed using the Tokyo Guidelines 2018; higher incidence of postoperative complications; and more hospitalization days than those in the non-DLC group. Multivariate analysis revealed that male, CAR (≥3.20), and pericholecystic fat hyperdensity on computed tomography (CT) were independent predictors of DLC. We developed a predictive scoring system for DLC based on these three factors (cutoff value, 2.0; area under the curve, 0.75; sensitivity, 71.7%; and specificity, 70.5%).CAR could predict DLC independently in AC patients. We identified male gender, CAR, and pericholecystic fat hyperdensity on CT as predictive factors for DLC and established a preoperative prediction system based on these three factors.

BackgroundPreoperative systemic inflammation has been reported to predict survival in patients with various cancers. Especially for colorectal liver metastasis (CRLM), the prognosis is poor despite therapeutic advances in the field. Here we aimed to evaluate the prognostic role of lymphocyte-to-C-reactive protein (CRP) ratio (LCR) in patients with CRLM after hepatic resection.MethodsThis retrospective study included 104 patients who underwent hepatic resection for CRLM over a period of 11 years, from October 2010 and October 2021, at the National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan. The association between clinicopathological variables, including various inflammation biomarkers [LCR, platelet-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), CRP-to-albumin ratio (CAR), and prognostic nutritional index (PNI)], and overall survival of the patients was investigated using univariate and multivariate analyses. ResultsThe optimal cut-off values of each biomarker by receiver operating characteristic analysis were as follows: LCR, 12,720; PLR, 150; NLR, 4; CAR, 0.023; and PNI, 44.8. The 1, 3, and 5 year overall survival rates were 97.0%, 71.3%, and 56.8%, respectively. In the univariate analysis, LCR < 12,720, PLR < 0.14, body mass index < 24, carbohydrate antigen 19-9 ≥ 37 U/ml, multiple tumors, and the largest hepatic tumor ≥ 5 cm were significant predictive factors. The multivariate analysis revealed that LCR < 12,720 [hazard ratio (HR): 2.156, 95% confidence interval (CI): 1.060–4.509, p = 0.034] and multiple tumors (HR: 2.336, 95% CI: 1.125–4.925, p = 0.023) were independent predictors of overall survival, whereas other inflammation biomarkers including NLR, PLR, CAR and PNI were not significant.ConclusionsThus, LCR could be an independent prognostic predictor in patients with CRLM after hepatic resection. Therefore, the assessment of LCR as a biomarker will help in the planning of treatment strategy including surgery and adjuvant therapies.

Background The prognostic nutritional index, a marker of nutritional status and systemic inflammation, is a known biomarker for various cancers. However, few studies have evaluated the predictive value of the prognostic nutritional index in patients with biliary tract cancer. Therefore, we investigated the prognostic significance of the prognostic nutritional index, and developed a risk-stratification system to identify prognostic factors in patients with biliary tract cancer. Methods Between July 2010 and March 2021, 117 patients with biliary tract cancer were recruited to this single-center, retrospective study. The relationship between clinicopathological variables, including the prognostic nutritional index, and overall survival was analyzed using univariate and multivariate analyses. A P Results The median age was 75 (range 38–92) years. Thirty patients had intrahepatic cholangiocarcinoma; 29, gallbladder carcinoma; 27, distal cholangiocarcinoma; 17, ampullary carcinoma; and 13, perihilar cholangiocarcinoma. Curative (R0) resection was achieved in 99 patients. In univariate analysis, the prognostic nutritional index ( 20 U/mL), preoperative cholangitis, tumor differentiation, operation time (≥ 360 min), and R1–2 resection were significant risk factors for overall survival. The prognostic nutritional index (P = 0.027), lymph node metastasis (P = 0.040), and tumor differentiation (P = 0.006) were independent prognostic factors in multivariate analysis. A combined score of the prognostic nutritional index and pathological findings outperformed each marker alone, in terms of discriminatory power. Conclusions The prognostic nutritional index, lymph node metastasis, and tumor differentiation were independent prognostic factors after surgical resection in patients with biliary tract cancer. A combined prediction model using the prognostic nutritional index and pathological findings accurately predicted prognosis, and can be used as a novel prognostic factor in patients with biliary tract cancer.

Introduction: We evaluated the prognostic significance of the preoperative albumin-to-globulin ratio (AGR) in patients with hepatocellular carcinoma (HCC) with various liver etiologies. Methods: We retrospectively analyzed 157 patients with HCC between July 2010 and February 2021. The relationship between clinicopathological variables was investigated using univariate and multivariate analyses. Statistical significance was set at p < 0.05. Results: The mean overall survival (OS) was 24.5 months. The 1-, 3-, and 5-year OS rates were 90.4%, 81.2%, and 68.7%, respectively. Patients were classified into 2 groups: AGR n = 43) and AGR ≥1.16 (high-AGR group; n = 114). In univariate analysis, OS was significantly reduced in patients with a low AGR (AGR p = 0.030) and microvascular invasion (2.268 [1.019–5.169]; p = 0.045) were independent predictors of OS. Discussion/Conclusion: A low AGR was significantly associated with poor OS in patients with HCC, regardless of liver etiology. This may assist in treatment stratification and better management of patients with HCC.

Background/aim Inflammation-based prognostic scores are proven prognostic biomarkers in various cancers. This study aimed to identify a useful prognostic score for patients with biliary tract cancer (BTC) after surgical resection. Patients and methods This retrospective study recruited 115 patients with BTC during 2010-2020. The relationship between clinicopathological variables, including various prognostic scores and overall survival (OS), was investigated using univariate and multivariate analyses. Results BTC included 58 cholangiocarcinoma, 29 gallbladder carcinoma, 16 ampullary carcinoma, and 12 perihilar cholangiocarcinoma cases. A significant difference was detected in OS of patients with a Japanese modified Glasgow prognostic score (JmGPS) 0 (n=62) and JmGPS 1 or 2 (high JmGPS) (n=53). In the multivariate analysis, tumour differentiation (p=0.014) and a high JmGPS (p=0.047) were independent prognostic factors. Conclusion The high JmGPS was an independent prognostic predictor after surgical resection and was superior to other prognostic scores.

The rate of local and anastomotic recurrence after curative resection for colon cancer is quite low, at 2.1%. We describe an anastomotic recurrence that rapidly increased after transverse colon cancer resection. An 80-year-old man underwent laparoscopic- assisted transverse colon resection with D3 lymph node dissection. The pathological diagnosis was pT4aN1bM0, pStage Ⅲb. We diagnosed the patient with anastomotic recurrence and liver metastasis 4 months after the procedure based on PET-CT findings. Partial colon resection(small intestine and stomach combined)was performed at 6 months after the procedure. The patient's quality of life(QOL)was reduced by complications after the second procedure and continuing with chemotherapy became difficult. Although the prognosis of curative resection of local and anastomotic recurrence after transverse colon cancer surgery can be good, combined resection of an adjacent organ can result in a decline in patient QOL. Surgical intervention should be minimally invasive and neo-adjuvant chemotherapy might offer 1 option.

This study was performed to determine the prognostic value of lymphocyte-to-CRP ratio after curative resection for hepatocellular carcinoma.Between July 2010 and October 2021, 173 consecutive patients (144 male, 29 female) who underwent surgical resection for pathologically confirmed hepatocellular carcinoma were included in this retrospective study. Cox regression analysis was used to evaluate the relationship between clinicopathological characteristics and recurrence-free survival (RFS) and overall survival (OS). A P-value of0.05 was considered statistically significant.The patients (mean age, 71 years) were stratified into high (≥9,500, n = 108) and low (9,500, n = 65) lymphocyte-to-CRP ratio groups. The low lymphocyte-to-CRP ratio group had significantly worse RFS and OS. Low lymphocyte-to-CRP ratio (hazard ratio [HR], 1.865; 95% confidence interval [CI], 1.176-2.960; P = 0.008), multiple tumors (HR, 3.333; 95% CI, 2.042-5.343; P0.001), and microvascular invasion (HR, 1.934; 95% CI, 1.178-3.184; P = 0.009) were independently associated with RFS, whereas low albumin-to-globulin ratio (HR, 2.270; 95% CI, 1.074-4.868; P = 0.032), α-FP of ≥25 ng/mL (HR, 2.187; 95% CI, 1.115-4.259; P = 0.023), and poor tumor differentiation (HR, 2.781; 95% CI, 1.041-6.692; P = 0.042) were independently associated with OS. Lymphocyte-to-CRP ratio had a higher area under the curve (0.635) than other inflammation-based markers (0.51-0.63).Lymphocyte-to-CRP ratio is superior to other inflammation-based markers as a predictor of RFS in patients with surgically resected hepatocellular carcinoma.

A woman in her early 50s underwent abdominoperineal resection with left lateral lymph node resection for advanced rectal cancer. The pathological diagnosis was RC, RbP, well-differentiated, type 5, 65×47mm, pT3(A), pN0(0/40), M0, pStage Ⅱ. The local recurrence discovered under the perineal skin 2 months later was treated by resecting the tumor and both inguinal lymph nodes. Adjuvant chemotherapy containing UFT plus LV was also initiated for 6 months. She remains free of recurrence 1 year after resection of the local recurrence.

The patient was a man in his early 30s. He underwent sigmoidectomy with D3+ #216 for advanced sigmoid colon cancer with metastatic para-aortic lymph nodes. The pathological diagnosis was colon cancer(S), type 2, moderately differentiated, pT4a(SE), pN3(19/33), pM1a(LYM), pStage IV , KRAS wild-type, EGFR(+). He received FOLFOX plus bevacizumab(Bmab) as adjuvant chemotherapy. One year postoperatively, he experienced recurrence as multiple lung metastases. FOLFIRI plus panitumumab, SOX plus Bmab, CapeOX, nivolumab and FOLFIRI plus ramucirumab were then administered. The patient has survived for 4 years and 11 months from operation.

We experienced 63 patients with non‑inflammatory disease who underwent single‑incision laparoscopic cholecystectomy (TANKO‑LC. Herein we report the procedure of operation and the short‑term results. We compared 63 cases of TANKO‑LC with 109 cases of non‑inflammatory conventional laparoscopic cholecystectomy (S‑LC within the same period. At first our standard procedure was to insert multiple trocars in the abdominal cavity through a single wound；now we insert only a single trocar all cases. In the 63 cases investigation 3 cases required trocar addition and one case converted to open surgery. Intra and postoperative complications were recognized in 2 cases (port‑site infection. No significant complications were recognized. In comparing the TANKO‑LC group and the S‑LC group the operation time was intentionally longer in the TANKO‑LC group (TANKO‑LC group：118 min S‑LC group：90 min but there were no differences in the blood loss the rates of intra and postoperative complications and the conversion rate. Laparoscopic cholecystectomy is a standard operation for gallbladder removal but single‑incision laparoscopic cholecystectomy is considered a useful operation with the same low operative complication rate yet more satisfactory cosmetic results.

症例1:35歳,男性. 主訴:特になし. 現病歴:平成16年1月,人間ドックの腹部エコー検査にて 膵頭部に嚢胞性病変を指摘された.3月精査目的で当科紹 介となった. 既往歴:7歳 脾門リンパ節炎,14歳 十二指腸潰瘍,24歳 気管支喘息. 現症:腹部は平坦,軟. 入院時検査所見:血液,生化学検査では異常を認めなかっ た.腫瘍マーカーにおいては,CEA 1.1ヘ/ml DUPAN-2 25未満U/mlで正常であったが,Span-1が58U/ml,CA19-9 が139.2U/mlと上昇を認めた. 腹部US所見:膵頭部~体部に直径47.6mm大の多房性の嚢 胞性腫瘍を認め,一部は壁在結節様であった. EUS 所見:膵頭部の腫瘍は44×49mm大で隔壁を持つ嚢胞 性病変として描出された.内部は不均一であった. 腹部CT所見:膵体部頭側に突出して5×5cm大の多房性 嚢胞性病変を認めた.比較的厚い被膜,隔壁を有している が,内部に明らかな充実部分は認めなかった.Dynamic study にて隔壁に早期濃染を認めた(図1a). MRI(MRCP)所見:膵体部の頭側に径46mm大の分葉状の 腫瘤性病変を認めた.T1強調像にてやや高信号,T2強 調像にてやや低信号を呈していた.信号強度から嚢胞内の 性状は比較的粘稠度が高いと考えられた.主膵管との連続 性は指摘できず,主膵管の拡張も見られなかった. 血管造影:腫瘍濃染などの異常は認めなかった. 膵リンパ上皮嚢胞の2例 濱 野 亮 輔*,稲 垣 優,木 村 裕 司,磯 田 健 太, 北 田 浩 二 ,西 江 学,野 村 長 久,徳 永 尚 之, 高 橋 健 司 ,宮 宗 秀 明,常 光 洋 輔,大 塚 眞 哉, 三 好 和 也 ,岩 川 和 秀,高 橋 正 彦,岩 垣 博 巳

2005年1月から2009年12月までの5年間に当院外科で経 験した大腸癌同時性肝転移54例を対象とし,1壁深達度, 2リンパ節転移,3腹膜播種,4遠隔転移,5肝転移分類, 6Grade 分類,7治療法別分類(肝切除群:肝切除+化学 療法,化学療法群:化学療法単独,無治療群)についてそ れぞれ臨床病理学的に検討した.なお,患者背景について は表1に示した.肝切除群症例(肝切除+術前・術後化学 療法)の術式等については表2に示したが,肝転移巣同時 切除(simultaneous resection:1期手術)が6例,大腸切 除後肝転移巣切除(staged resection:2期手術)が5例で あった.また,肝切除群においては,術後または術前後に 化学療法が施行されていた.化学療法の内容は様々で一定 の傾向はなく,肝動注,経口,全身化学療法が重複して施 行されていた(表3).当院では,可能であれば手術を第一 選択としており,大腸癌治療ガイドラインと同様,耐術可 能で,十分な残肝機能があり,肝転移巣が遺残なく切除可 能(RFAも含む)で原発巣が制御されている場合に行って いる.肝門部リンパ節転移陽性を含む遠隔転移症例は肝切 除の適応から除外している.また,肝切除群11例中3例に ラジオ波焼灼術(RFA)を併用した(表2).RFAは切除 しきれない腫瘍に対して術中に併用した.手術適応外の症 例において,可能であれば基本的には化学療法を施行して 当院における大腸癌同時性肝転移症例の臨床病理学的検討 宮 宗 秀 明*,岩 川 和 秀,稲 垣 優,木 村 祐 司, 西 江 学 ,濱 野 亮 輔,徳 永 尚 之,常 光 洋 輔, 大 塚 眞 哉 ,岩 垣 博 巳

Phlegmonous gastritis is a rare inflammatory lesion in which bacterial infection occurs in the gastric wall. A 92-year-old man was admitted to the medical ward due to early gastric cancer. The patient received endoscopic submucosal dissection (ESD), and he complained of sudden-onset upper abdominal pain the day after ESD. On physical examination he showed rebound tenderness in the upper abdomen. The white blood cell count was 16,100/μl, and an abdominal CT-SCAN showed diffuse and irregular thickening of the gastric wall. At emergency operation, a subtotal gastrectomy was performed, and the patient had an uneventful recovery.

A 77-year-old woman was admitted to our hospital due to abdominal pain and body weight loss. A palpable mass the size of an infant's head was tender on palpation and identified as an epigastric lesion. Colonoscopic examination revealed stenosis of the transverse colon, although no intraluminal growth of the tumor was found. The histologic findings of the biopsy material were poorly differentiated and/or undifferentiated cells. Abdominal CT scan showed an irregular-shaped tumor with a diameter of 10cm invading the stomach and jejunum. We performed an operation under a diagnosis of extramurally growing cancer or malignant lymphoma of the colon. Partial resection of the transverse colon was done by distal gastrectomy and partial resection of the jejunum. Histologic examination of the operative specimens revealed moderately differentiated adenocarcinoma of the transverse colon, prominently proliferating into the surrounding tissues. The finding of a long stenotic lesion and extramural compression by colonography are characteristic of this tumor, based on a review of 43 literature reports in Japan.

We experienced 20 patients with distal bile duct carcinoma from May, 1997 to December, 2007. The male/female ratio was 11/9 and the average age was 69.6 years. The operative procedures were as follows : pancreaticoduodenectomy (PD), 9 ; pyrolus preserving pancreaticoduodenectomy (PPPD), 8 ; subtotal stomach preserving pancreaticoduodenectomy (SSPPD), 2 and hepatico-jejunostomy without resection, 1. We performed a clinicopathological study on 16 patients with distal bile duct carcinoma, excluding 3 operation-related deaths and 1 unresectable case. The cumulative survival rate was 70% at 3 years and 11% at 5 years. The 3-year survival rates at fStageII, fStageIVa and fStageIVb were 100%, 80% and 0%, respectively. Log-rank analysis revealed that pathological pancreatic and duodenal invasion and curative resectability may be prognostic factors, while lymph node metastasis and perineural and stump invasion did not affect prognosis. Six recurrences in the 11 curative resection cases (54.5%) were observed ; therefore, postoperative systemic chemotherapy is warranted to curtail recurrence in advanced distal bile duct carcinoma.

A 58-year-old man was diagnosed as having descending colon cancer and underwent a left colectomy with D3 node dissection and end-to-end anastomosis reconstruction. The accessory middle colic artery was secured as a feeding artery, and the middle colic artery was preserved. Diet was started on postoperative day 5 (POD5), and nausea and vomiting appeared on POD10. An upper gastrointestinal series revealed to-and-fro peristalsis in the third portion of the duodenum and dilatation of the proximal duodenum. Abdominal CT showed that the second portion of the duodenum was markedly dilated and the third portion was compressed by the superior mesenteric artery (SMA). As a result, he was diagnosed with post-operative superior mesenteric artery syndrome (SMAS) and treated with conservative therapy. The symptoms improved with a nasogastric tube, and he started to eat after POD26, followed by a successful outcome.

今回われわれは稀な骨盤腔後腹膜に発生した巨大な悪性末梢神経鞘腫瘍（MPNST）の1例を経験したので報告する．症例は74歳，男性．右下腹部腫瘤を主訴に2006年3月来院．CT検査，MRI検査にて骨盤腔内後腹膜に境界明瞭な約15cm大の腫瘍を認め，2006年5月手術施行した．腫瘍は巨大で骨盤腔右側を占めていたが，周辺臓器への浸潤は認めず，経腹的に腫瘍を完全摘出した．摘出腫瘍は大きさ15.0×10.0×8.5cmで重量640gであった．病理組織学診断で長紡錘状腫瘍細胞の粗な増殖がみられ，核異型，分裂像を認めた．免疫染色でS-100は陰性であったが，NSE，vimentin，MIB-1が陽性を示していたことからMPNSTと診断された．術後経過は良好で術後17日目に退院となった．術後2年経過した現在再発は認めていない．

We report a rare case of a very large nonfunctioning endocrine tumor of the pancreas without malignant histological features. A 63-year-old woman referred for appetite loss and general fatigue was found to have a tumor in the pancreas head. Computed tomography demonstrated a well-defined pancreatic tumor 45mm in diameter with hypervascular staining in the pancreas head. Angiography showed a hypervascular tumor of the pancreas head and a dilatation of the anterior superior and posterior superior pancreaticoduodenal arteries. The preoperative diagnosis was an endocrine tumor of the pancreas, with undeniable malignancy. Pylorus-preserving pancreaticoduodenectomy was performed. The histopathological diagnosis was a benign nonfunctioning endocrine tumor of the pancreas based on immunohistochemical staining for Chromogranin A, Synaptophysin, and NSE, but not for hormones. The tumor revealed a low labeling index (

The aim of the present study was to investigate the safety and immunological responses of personalized peptide vaccination in combination with oral administration of a 5-fluorouracil derivative (TS-1) in advanced gastric or colorectal carcinoma patients. Eleven patients (four with gastric cancer and seven with colorectal cancer) who failed to improve by prior TS-1-based chemotherapies were enrolled in this study. Peptides to be administered to patients were determined based on the presence of peptide-specific cytotoxic T lymphocyte (CTL) precursors in peripheral blood mononuclear cells and peptide-specific IgG in the plasma of cancer patients. Patients were vaccinated with peptides (a maximum of four) biweekly in combination with or without three different doses of TS-1 (20, 40 and 80 mg/m(2)/day). Although grade 3 toxicity, including anemia (one patient) and neutropenia (one patient) were observed, the combination therapy was generally well tolerated. An increase in peptide-specific IgG after the sixth vaccination was observed in the vast majority of patients irrespective of the dose of TS-1 used. In contrast, an increase in peptide-specific interferon-gamma production by CTL was most evident in patients who were administered the highest dose of TS-1. Furthermore, in the patients who received 80 mg/m(2)/day TS-1, CTL-mediated cytotoxicity against cancer cells was maintained at the prevaccination level. These results indicate that administration of the standard dose (80 mg/m(2)/day) of TS-1 in combination with a personalized peptide vaccination does not necessarily impede immunological responses in cancer patients, and could actually maintain or augment them.

Colovesical fistula (CVF) resulting from colon diverticulosis is a comparatively rare disease, and neither the diagnosis nor treatment has been established. Our experience with CVF due to sigmoid diverticulitis over a 9-year period was reviewed to clarify the clinical presentation and diagnostic confirmation. Ten patients with CVF were identified in this period, and chief complaints, laboratory findings, presenting symptoms, diagnostic investigations, and subsequent treatments were reviewed. Preoperative urinalysis showing bacteriuria (100%) was the most common presentation, followed by fecaluria (40%), abdominal pain (40%), pneumaturia (30%), hematuria (30%), pain on urination (30%), pollakiuria (10%), and dysuria (10%). The abilities of various preoperative investigations to identify CVF were: computed tomography (CT), 88.9%; magnetic resonance imaging, 40%; cystoscopy, 30%, and gastrografin irrigoscopy, 22.2%. Colonoscopy (0%) was not diagnostic. Bowel resection was performed in nine of ten patients. When inflammation was intense, covering ileostomy was performed, and an omental plasty was placed between the bowel anastomosis and bladder. When CVF is suspected, we recommend CT followed by colonoscopy and cystoscopy as a first-line investigation to rule out malignancy as a cause. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management. Primary colic anastomosis appears to be safely performed by applying omental plasty and covering ileostomy.

Bacteria isolated from surgical infections during the period from April 2010 to March 2011 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 631 strains including 25 strains of Candida spp. were isolated from 170 (81.7%) of 208 patients with surgical infections. Four hundred and twenty two strains were isolated from primary infections, and 184 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. such as Enterococcus faecalis, Enterococcus faecium, and Enterococcus avium was highest, followed by Streptococcus spp. such as Streptococcus anginosus and Staphylococcus spp. such as Staphylococcus aureus, in this order, from primary infections, while Enterococcus spp. such as E. faecalis and E. faecium was highest, followed by Staphylococcus spp. such as S. aureus from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Pseudomonas aeruginosa in this order, and from surgical site infection, E. coli and R aeruginosa were most predominantly isolated, followed by E. cloacae and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rates of Parvimonas micra, Eggerthella lenta, Streptococcus constellatus, Gemella morbillorum, and Collinsella aerofaciens were the highest from primary infections, and the isolation rate from surgical site infection was generally low. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by, Bacteroides fragilis and Bacteroides ovatus, and from surgical site infection, B. fragilis was most predominantly isolated, followed by Bacteroides thetaiotaomnicron, in this order. In this series, vancomycin-resistant MRSA (methicillin-resistant S. aureus), vancomycin-resistant Enterococcus spp. and multidrug-resistant P. aeruginosa were not observed.

Purpose: Dendritic cells (DCs) are attractive effectors for cancer immunotherapy because of their potential to function as professional antigen-presenting cells for initiating cellular immune responses. The tumor suppressor gene p53 is pivotal in the regulation of apoptosis, and ∼50% of human malignancies exhibit mutation and aberrant expression of p53. We investigated the antitumor effect of intratumoral administration of bone marrow-derived dendritic cells transduced with wild-type p53 gene. Experimental Design: We examined whether intratumoral administration of DCs infected with recombinant adenovirus expressing murine wild-type p53 (Ad-mp53) could induce systemic antitumor responses against mutant p53-expressing tumors, highly immunogenic MethA, or weakly immunogenic MCA-207 implanted in syngeneic mice. Results: Accumulation of wild-type p53 protein in bone marrow-derived murine DCs could be successfully achieved by Ad-mp53 infection. Treatment with intratumoral injection of Ad-mp53-transduced DCs caused a marked reduction in the in vivo growth of established MethA and MCA-207 tumors with massive cellular infiltrates. Administration of p53-expressing DCs suppressed the growth of both injected MCA-207 tumors and untreated distant MCA-207 tumors, but not unrelated Lewis lung carcinoma tumors, suggesting the augmentation of systemic immunogenicity against MCA-207 tumor cells. Moreover, intratumoral injection of p53-expressing DCs had a greater antitumor effect than did s.c. immunization. Conclusions: Our results indicate that intratumoral administration of DCs expressing murine wild-type p53 leads to significant systemic immune responses and potent antitumor effects in mutant p53-expressing murine cancer models. These findings raise the possibility of using this strategy of intratumoral injection of p53-expressing DCs for human cancer treatment.

Adenovirus-mediated wild-type p53 gene transfer induces apoptosis in a variety of human cancer cells. Although clinical trials have demonstrated that a replication-deficient recombinant adenovirus expressing the wild-type p53 gene (Ad-p53) is effective in suppressing growth of non-small cell lung cancer (NSCLC), we often experienced late resistance to this treatment. To elucidate the mechanism of late resistance to Ad-p53 in human lung cancer cells, we generated 5 different resistant variants from p53-susceptible H1299 NSCLC cells by repeated infections with Ad-p53. We first examined the transduction efficiency of adenoviral vector by Ad-LacZ transduction followed by X-gal staining in parental and 5 resistant H1299 cell lines. Their sensitivity to viral infection decreased in correlation with the magnitude of resistance, and Ad-p53-mediated tumor suppression could be restored by dose escalation of Ad-p53 in the resistant variants. The expression of Coxsackie and adenovirus receptor (CAR) and alphaV integrins, which are cellular receptors for attachment and internalization of the virus, respectively, was next investigated in these cell lines. Flow cytometry revealed that alphaVbeta3 and alphaVbeta5 integrin expression was consistent, while p53-resistant cell lines showed that diminished CAR expression correlated with the magnitude of the resistance. Our results demonstrated that decreased CAR expression could be one of the mechanisms of late resistance to Ad-p53, which may have a significant impact on the outcome of adenovirus-based cancer gene therapy.

Background: Gene therapy is an innovative therapeutic approach for cancer. An adenoviral vector expressing the tumour suppressor p53 gene (Ad/p53) is currently under clinical evaluation for various cancers. We recently developed a binary adenoviral vector system that can express the strong proapoptotic gene Bax (Ad/PGK-GV16+Ad/GT-Bax: Ad/Bax). Aims: To evaluate the potential of Bax gene therapy for gastric cancer, we assessed its antitumour effect in comparison with that of p53. Methods: The human gastric cancer cell lines MKN-1, MKN-7, MKN-28, and MKN-45 were treated with Ad/Bax or Ad/p53, and cell viability, transgene expression, and caspase activation were assessed in vitro. To compare the antitumour effects of Ad/Bax and Ad/p53 treatment in vivo, subcutaneous tumours and peritoneal dissemination of MKN-45 cells were generated in nude mice. Each mouse underwent intratumoral or intraperitoneal administration of viruses and the growth of implanted tumours was observed after treatment. Results: Treatment with Ad/Bax and Ad/p53 resulted in marked Bax and p53 protein expression and effective apoptosis induction in MKN-1, MKN-7, and MKN-28 cells in vitro. In contrast, MKN-45 cells showed resistance to Ad/p53 and only treatment with Ad/Bax resulted in activation of caspase 3 expression and massive apoptosis. Ad/Bax treatment was more effective in suppressing both subcutaneous and peritoneally disseminated MKN-45 tumours compared with Ad/p53 treatment. Conclusion: Ad/Bax treatment significantly inhibited the growth of even p53 resistant gastric cancer in vitro and in vivo. Therefore, adenovirus mediated Bax gene transfer may be useful in gene therapy for gastric cancers.

To analyze the mechanism of the antitumor effect of an adenoviral vector expressing the p53 tumor suppressor (Ad-p53) in vivo, we quantitatively assessed p53-targeted gene expression and visualized transcriptional activity of p53 in tumors in nude mice treated with Ad-p53. Human lung cancer (H1299) xenografts established in nude mice were treated by intratumoral administration of Ad-p53. The levels of expression of exogenous p53 and p53-targeted genes p21, MDM2, Noxa, and p53AIP1 were quantified by real-time reverse transcription-PCR (RT-PCR) and induction of apoptosis was observed histochemically on days 1–3, 7, and 14 after treatment. Expression of mRNA of exogenous p53 and p53-targeted genes (except p53AIP1) was at its maximum 1 day after Ad-p53 treatment and then decreased rapidly; apoptosis was evident in situ 2–3 days after treatment. We developed a noninvasive and simple method for monitoring the transcriptional activity of exogenous p53 following intratumoral administration of Ad-p53 in nude mice. We established H1299 cells that express the green fluorescent protein (GFP) reporter gene under the control of p53-responsive p21 promoter (i.e., the p53R-GFP reporter system). Xenografts of these cells in nude mice were treated by intratumoral administration of Ad-p53, and the transcriptional activity of exogenous p53 could be visualized as intratumoral GFP expression in real time by 3-CCD camera. Expression of GFP was maximal 3 days after treatment and decreased remarkably by 7 days after treatment. We demonstrated that Ad-p53 treatment rapidly induced p53-targeted genes and apoptosis in tumors and succeeded in visualizing p53 transcriptional activity in vivo. We also found that Ad-p53 infection induced phosphorylation of p53 at Ser46 in p53-sensitive H1299 cells in vitro but not in p53-resistant H226Br cells, suggesting that phosphorylation of Ser46 is involved in p53-dependent apoptosis. Our data indicate that quantitative analysis of p53-targeted gene expression by real-time quantitative RT-PCR and visualization of p53 transcriptional activity in fresh xenografts by using the p53R-GFP reporter system may be useful in assessing the mechanisms of the antitumor effects of Ad-p53 and novel therapeutic approaches.

A Case of Resected Cholangiolocellular Carcinoma during Treatment for Lung Cancer Cholangiolocellular carcinoma is an extremely rare malignant primary liver tumor, accounting for less than 1% of primary liver tumors. We herein report a case of cholangiolocellular carcinoma during treatment for lung cancer. A woman following up after operation for lung cancer was found to have a solitary hepatic tumor in the left lobe of the liver at an abdominal computed tomography checkup. It showed early enhancement with hypovascular area of the center in the arterial phase and enhancement contrast retention in the delayed phase. The tumor was seen as a hypointense nodule in the hepatocellular phase of EOB magnetic resonance imaging. We diagnosed liver metastasis of lung cancer with differential diagnosis of cholangiocellular carcinoma. We performed extended left lobectomy of the liver. Histological and immunohistochemistry findings were compatible with cholangiolocellular carcinoma./p>

Radiofrequency ablation (RFA) therapy combined with hepatectomy was performed in 5 patients with synchronous liver metastases of colorectal cancer. RFA of liver metastases was performed using a Cool-tip electrode (Radionics; Burlington, MA, USA). The ablation time used in each session varied according to the tumor size and intraoperative impedance. In 2 patients, hepatectomy and resection of the colorectal primary lesion were performed synchronously. In patients with multiple liver metastases, relative curative resection was performed using the complementary RFA. In the other 3 patients, synchronous hepatectomy was considered difficult and systematic chemotherapy was performed after resection of the colorectal primary lesion. After systematic chemotherapy, the range of hepatectomy was restricted for liver injury, but relative curative resection was performed using RFA therapy. Computed tomography performed after hepatectomy showed that the region that underwent RFA appeared necrotic with a safety margin. The average observation period was 25 months (maximal survival period, 50 months) and 3 of the patients are alive.

A 25-year-old man with RS rectal cancer received a radical resection of the original tumor and lymph node dissection. Oral tegafur/uracil (UFT)/Leucovorin (LV) therapy has been used for adjuvant chemotherapy, as the pathological Stage was T3N1M0, Stage IIIa. After 10 months from operation, multiple liver metastases were recognized and not resectable. So a systemic chemotherapy by mFOLFOX6+bevacizumab was begun via CV port. After 5 courses of mFOLFOX6+bevacizumab, abdominal CT revealed liver metastases showed remarkable reduction in size. Hepatic resection of S6 segment was enforced, and the patient uneventfully discharged. Pathological findings of S6 segment revealed no residual cancer cells, indicating the histological effect of mFOLFOX6+bevacizumab was Grade 3. And no liver damage was recognized.