Hidehisa Yamada

Somatic Mutations of the APC Gene in Primary Breast Cancers

APC gene mutations play an important role in the initiation step of colorectal carcinogenesis in both familial adenomatous polyposis (FAP) patients and non-FAP patients. Although the APC gene is expressed in most tissues, including the lung, liver, kidney, and mammary gland, its somatic mutations have rarely been found in primary tumors affecting these organs. We have developed a sensitive yeast-based assay for screening almost the entire coding region of the APC gene. By this method, we have been able to detect somatic mutations of the APC gene in 57% of colorectal cancers and none in non-small cell lung cancers. Interestingly, the assay detected somatic APC gene mutations in 18% of breast cancers, in which APC gene mutation was previously considered rare. In the breast cancers, most of the APC mutations were distributed outside the mutation cluster region that has been advocated for colorectal cancers. We also noted a difference in the mutation pattern of the APC between colorectal and breast cancers. In colorectal cancers, all base substitutions were observed at C residues (5 of 5), whereas in breast cancers the majority of them were found at G residues (4 of 5). Furthermore, APC mutations were observed at a significantly high frequency in advanced stages of primary breast cancers (TNM classification, P < 0.05; T category, P < 0.01). Our data suggest that the etiology of the APC mutations and their biological role in carcinogenesis may differ between colorectal and breast cancers.

Analysis of predictive factors for recurrence after hepatectomy for colorectal liver metastases.

Hepatectomy for liver metastases from colorectal cancer has recently received general acceptance as a safe, potentially curative treatment. Most patients, however, die of recurrent disease after hepatectomy. The predictive factors for recurrence after first resection of liver metastases have not yet been clarified. The authors aimed to determine the factors that can predict recurrence, especially hepatic-only recurrence after hepatectomy for colorectal liver metastases. Seventy-six patients who underwent liver resection of colorectal metastases were studied retrospectively. Forty-seven (61.8%) of the patients had a recurrence. The patients’ disease-free survival after first hepatectomy and the second recurrence sites were univariately and multivariately analyzed using 16 clinicopathologic variables. Wall invasion, lymph node metastases, lymphatic invasion, venous invasion of the primary tumor, 24 months or longer disease-free interval after resection of the primary colorectal cancer, and bilateral liver metastases significantly influenced the disease-free survival (log-rank test:p<0.05). The multivariate analysis revealed that venous invasion of the primary tumor and bilateral hepatic metastases were independent risk factors for recurrence after hepatectomy. The liver was the only site of second recurrence in 23 patients. Patients with lymph node metastases and venous invasion of the primary tumor had a significant difference between hepatic-only and extrahepatic recurrence after first hepatectomy (chi-square test or Fishers’ exact test:p<0.05). Recurrence after hepatectomy was influenced more by factors associated with the primary colorectal cancer than factors surrounding the first liver metastases. Venous invasion of the primary colorectal cancer was the most important predictable factor for hepatic-only second recurrence.RésuméOn considère que la résection de métastases hépatiques provenant de cancer colorectal est un procédé acceptable, sur et potentiellement curateur. La plupart des patients, cependant, meurent de récidives après résection hépatique. Les facteurs prédictifs de récidive, après une première résection de métastases hépatiques, ne sont pas encore établis. Le but ici a été de déterminer les facteurs qui peuvent prédire la récidive, surtout les récidives hépatiques seules, après résection de métastases de cancer colorectal. On a étudié 76 patients ayant eu une résection de métastases d’origine colorectale de façon rétrospective. Quarante-sept (61.8%) patients ont récidivé. On a réalisé une analyse mono et multifactorielle des facteurs de survie sans maladie après une première résection et la deuxième récidive, selon 16 variables clinicopathologiques. L’envahissement pariétal, les métastases lymphatiques, l’envahissement des vaisseaux lymphatiques, l’envahissement veineux de la tumeur primitive, un intervalle sans maladie de 24 mois ou plus après résection du cancer colorectal primitif, et la bilatéralité des métastases ont significativement influencé la survie sans maladie (test de Log-Rank; p<0.05). L’analyse multifactorielle a révélé que l’envahissement veineux de la tumeur primitive et la bilatéralité des métastases étaient des facteurs indépendants de récidive après résection pour métastases. Le foie a été le site de récidive secondaire chez 23 patients. On a trouvé une différence significative entre les patients ayant des métastases ganglionnaires et un envahissement veineux à partir de leur tumeur primitive en ce qui concerne le site de leur récidive (hépatique seule ou extrahépatique) après la première résection hépatique (test de chi2 ou test de Fisher; p<0.05). La récidive après hépatectomie a été influencée par les facteurs en rapport avec le cancer primitif colorectal plus que par les facteurs concernant les récidives hépatiques. L’envahissement veineux du cancer colorectal est le facteur principal et le facteur prédictif le plus important pour récidive hépatique secondaire seule.ResumenEn la actualidad, se acepta que la hepatectomia constituye el tratamiento más eficaz, potencialmente curativo, de las mestástasis hepáticas de un cáncer colorrectal. Sin embargo, bastantes pacientes fallecen tras las hepatectomia, por recidiva de la enfermedad cancerosa. Hasta ahora, no se conocen los factores predictivos de recidiva tras la primera resección por metástasis hepáticas. Los autores intentan determinar qué factores pueden predecir la recidiva, especialmente en casos de recidivas exclusivamente hepáticas, tras hepatectomia por metástasis del cáncer colorrectal. Se analizaron retrospectivamente 76 pacientes hepatectomizados por metástasis de cáncer colorrectal. En 47 (61.8%) casos, se constataron recidivas metastásicas en el higado. Se analizaron mediante test uni y mulivariables, utilizando 16 variables clinico-patológicas, la supervivencia de los pacientes libres de enfermedad, tras la primera hepatectomía y la localización de las segundas recidivas metastásicas. La invasión parietal, los ganglios metastásicos, la invasión linfática, la invasión venosa del tumor primario (colorrectal), el intervalo libre de enfermedad tras la resección del cáncer colorrectal igual o superior a 24 meses y, la existencia de metástasis bilaterales en ambos lóbulos hepáticos, influyen significativamente en la supervivencia libre de enfermedad (log-rank test: p<0.05). El análisis multivariante demuestra que la invasión venosa del tumor primario y las metástasis hepáticas bilaterales constituyen factores de riesgo independientes para la recidiva tras hepatectomia. El higado, en 23 pacientes, fue la única localización de la segunda recidiva. Pacientes en los que el tumor primario produjo metástasis ganglionares e invasión venosa, presentaron diferencias significativas por lo que a las recidivas sólo hepáticas y extrahepáticas (tras la primera hepatectomia) se refiere (test de la chi al cuadrado o test de Fischer: p<0.05). La recidiva tras hepatectomia se debe más a las caracteristicas del cáncer primario colorrectal que a otros factores dependientes de las primeras metástasis hepáticas. La invasión venosa del cáncer primario colorrectal es el factor predictivo más importante por lo que se refiere a las recidivas de metástasis localizadas exclusivamente en el higado.

Surgical treatment of liver metastases from pancreatic cancer.

Pancreatic cancer is a disease with a poor prognosis. Most patients are diagnosed at an advanced and unresectable stage. Even if the primary cancer is radically removed, postoperative recurrence frequently occurs. Generally, metastatic liver tumors from pancreatic cancer are not indicated for surgical treatment. Here we evaluate the results of performing hepatectomy for liver metastases of pancreatic cancer. In our institute, six patients with liver metastases from pancreatic cancer were treated by partial hepatectomy. Overall 1-, 3- and 5-year survival rates of six patients after hepatectomy were 66.7%, 33.3% and 16.7%, respectively, and one patient was alive for 65.4 months. Performing a hepatectomy for liver metastases of pancreatic cancer, when combined with a pancreas resection, was recently considered to be a safe operation, and one that might offer prolonged survival for highly selected patients with curative resection of liver metastases. In the future, it will be necessary to develop new multi-modality therapies to improve the prognosis of pancreatic cancer.

Adult Intussusception Due to Enteric Neoplasms

Adult intussusception is an infrequent disease and the cause of intussusception differs between children and adults [1–3]. Many of the cases in adults are secondary to an underlying lesion and adult intussusception of the colon is most often secondary to a malignant tumor. There are no typical complaints, signs, or symptoms often associated with the chronic process of bowel obstruction. The diagnosis of adult intussusception is usually made by preoperative radiological and endoscopic examinations, or during laparotomy. Surgical resection or operative reintegration is required. The aim of this study was to retrospectively evaluate the preoperative diagnoses and surgical treatments of patients with adult intussusception in our hospital.

Development of a Yeast Stop Codon Assay Readily and Generally Applicable to Human Genes

We established a yeast-based method to screen chain-terminating mutations that is readily applicable to any gene of interest. Based on the finding that 18- to 24-base-long homologous sequences are sufficient for gap repair in vivo in yeast, we used a strategy to amplify a test-gene fragment with addition of 24-bp sequences homologous to both cut-ends of a yeast expression vector, pMT18. After co-transformation with the amplified fragment and the linearized pMT18, each yeast (Saccharomyces cerevisiae) cell automatically forms a single-copy circular plasmid (because of CEN/ARS), which expresses a test-gene::ADE2 chimera protein. When the reading frame of the test-gene contains a nonsense or frameshift mutation, truncation of the chimera protein results in lack of ADE2 activity, leading to formation of a red colony. By using a nested polymerase chain reaction using proofreading Pfu polymerase to ensure specificity of the product, the assay achieved a low background (false positivity). We applied the assay to BRCA1, APC, hMSH6, and E-cadherin genes, and successfully detected mutations in mRNA and genomic DNA. Because this method--universal stop codon assay--requires only 4 to 5 days to screen a number of samples for any target gene, it may serve as a high-throughput screening system of general utility for chain-terminating mutations that are most prevalent in human genetic diseases.

Single incision laparoscopic approach for esophageal achalasia: A case report

INTRODUCTION Esophageal achalasia is an uncommon, benign, neurodegenerative disease that induces a transit disorder characterized by incomplete lower esophageal sphincter relaxation. PRESENTATION OF CASE A 56-year-old woman with dysphagia was admitted to our hospital. An esophagography revealed flask-type achalasia. Endoscopy revealed a dilated esophagus and some resistance at the esophagogastric junction. We used a capped wound protector, common straight forceps, and hook-type electrocautery to perform transumbilical single incision laparoscopic Heller myotomy with Dor fundoplication (SILHD). The left liver lobe and cardia were pulled by a thread. A 6-cm Heller myotomy of the esophagus was performed with an additional 2-cm myotomy of the gastric wall. Dor fundoplication was performed to cover the exposed submucosa. Intraoperative endoscopy confirmed the adequacy of the myotomy and Dor fundoplication. There were no postoperative complications. An esophagography and an endoscopic examination did not reveal stenosis or reflux at 1-year follow-up, and the patient has been satisfactorily symptom free. DISCUSSION LHD is the most accepted surgical treatment for achalasia and has low invasiveness and long-term efficacy. SILHD for achalasia is a new approach and may provide improved cosmetics and less invasiveness compared with those by conventional LHD. The 1-year follow-up results in the present case are the longest reported to date. The evaluation of long-term results in a large-scale study is necessary in future. CONCLUSION SILHD can be safe, widely accepted, mid-term minimal invasive and cosmetically superior surgical procedure for achalasia.

Erratum to: Liquid-injection for preperitoneal dissection of transabdominal preperitoneal (TAPP) inguinal hernia repair

In the title the word ‘‘inguial’’ is correctly spelled ‘‘inguinal’’. On the first page, in the Abstract, 8th line, ‘‘preperitonal’’ should be ‘‘preperitoneal’’. At the bottom of the left column, first page, T. Mizota, N. Takemoto, H. Yamada, Y. Miyasaka NTT East Sapporo Hospital, Sapporo, Hokkaido, Japan e-mail: nori-take@pop16.odn.ne.jp should be changed to T. Mizota N. Takemoto H. Yamada Y. Miyasaka NTT East Sapporo Hospital, Sapporo, Hokkaido, Japan e-mail: tmizota@huhp.hokudai.ac.jp N. Takemoto e-mail: nori-take@pop16.odn.ne.jp On the second page, left column, 4th paragraph, first line, delete ‘‘to’’. On the fifth page, left column, first paragraph, 9 line, change ‘‘safely’’ to ‘‘safety’’. In Reference 8, change ‘‘Naoki M’’ to ‘‘Matsumura N’’. The online version of the original article can be found under doi:10. 1007/s00464-014-3703-7.

Long-term Survival after Local Recurrence from Gastric Cancer: Report of a Case

症例は63歳の男性で, 1994年8月3日胃癌に対して幽門側胃切除術を施行した. 総合所見は中分化型腺癌, fT1 (SM), N1, H0, P0, M0, fStage IBであった. 1996年7 月の腹部CT で胃十二指腸吻合部から膵頭部前面にかけて腫瘤を認め, その後徐々に増大傾向を示したが他部位に再発巣を認めず1997年11月6日膵頭十二指腸切除術を施行した. 腫瘤は胃十二指腸吻合部から膵頭部にかけて一塊となっており膵との境界は不明瞭で剥離困難であった. 病理学的検査で胃癌の局所再発と判定された. 再発切除後6年6か月経過した現在, 再発徴候なく健在である. 本例は再発胃癌に対して膵頭十二指腸切除術を施行し長期生存が得られたまれな症例と考え若干の文献的考察を加え報告した.