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Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from the gastrointestinal tract, mostly from the stomach. GISTs are derived from the myenteric interstitial cells of Cajal and are caused by several mutations in the c-kit and platelet-derived growth factor receptor genes. Clinically, GISTs are detected by endoscopic and imaging findings and are diagnosed by immunostaining. Surgery is the first line of treatment, and if the tumor is relatively small, minimally invasive surgery such as laparoscopy is performed. In recent years, neoadjuvant therapy has been administered to patients with GISTs that are suspected of having a large size or infiltration to other organs. Postoperative adjuvant imatinib is the standard therapy for high-risk GISTs. It is important to assess the risk of recurrence after GIST resection. However, the effect of tyrosine kinase inhibitor use will vary by the mutation of c-kit genes and the site of mutation. Furthermore, information regarding gene mutation is indispensable when considering the treatment policy for recurrent GISTs. This article reviews the clinicopathological characteristics of GISTs along with the minimally invasive and multidisciplinary treatment options available for these tumors. The future perspectives for diagnostic and treatment approaches for these tumors have also been discussed.

Background A gastrointestinal stromal tumor (GIST) is a mesenchymal tumor of the gastrointestinal tract that is most commonly found in the stomach. Recurrence of GISTs mostly occurs in the liver or peritoneum, and in most cases, multiple metastases occur. As a solitary peritoneal metastasis is rare, an appropriate treatment strategy has not been established. Here, we report a case of solitary peritoneal metastasis after complete resection of gastric GIST. Case summary A 76-year-old woman was diagnosed with stomach GIST and underwent laparoscopic local resection using the CLEAN-NET method. As the recurrence risk was intermediate, adjuvant imatinib therapy was not administered. Two years after surgery, routine computed tomography revealed an abdominal mass between the dorsal side of the right hepatic lobe and right kidney. Other imaging tests did not reveal any abnormalities. Laparoscopic observation showed that the tumor was located at the retroperitoneum, and intraperitoneal dissemination was not found. Therefore, we performed laparoscopic tumor resection. Immunohistochemically, the tumor was positive for c-kit and CD34 and had a relatively high mitotic index and MIB-1 Labeling index. We administered adjuvant imatinib therapy. There was no evidence of recurrence 3 years after the operation. Conclusion This is the first reported case of a solitary recurrence of GIST in the peritoneum treated with complete laparoscopic resection.

A 55-year-old woman with a history of right hepatic lobectomy via a Benz incision presented for evaluation of a new abdominal bulge in the right upper quadrant. We diagnosed an incisional hernia, but because we could neither reduce the hernia contents nor locate the orifice, we performed a laparoscopic evaluation. Laparoscopy revealed subcostal herniation of the greater omentum via a 2-cm defect on the caudal side of the right ribs, which we repaired using a Ventralex ST Hernia Patch. Laparoscopic placement of this mesh with straps allowed for reliable deployment, fixation, and confirmation of defect closure, including the cranial aspect-often a major challenge in subcostal hernia repair.

Highlights • We underwent two emergency laparotomies for FOP patient. • Ossification of the incision did not occur within 6 months. • Two laparotomies could be performed safely in a patient with FOP., Introduction Fibrodysplasia ossificans progressiva (FOP) is a disorder causing progressive heterotopic ossification of muscles, tendons, and ligaments. Invasive procedures such as surgery should be avoided, because physical stimulation causes heterotopic ossification. Presentation of case A 40-year-old Japanese man with FOP was transported to our hospital with sudden abdominal pain. Emergency surgery was performed because a computed tomography scan showed the presence of intraabdominal free air. We diagnosed peritonitis due to perforation of Meckel's diverticulum and performed a small intestinal resection. The day after surgery, airway obstruction was recognized, and tracheostomy was required. Six months after surgery, a strangulated small bowel obstruction developed, and a second laparotomy was performed. As the patient continued to have difficulty swallowing, we constructed a gastrostomy at the time of the second surgery. He was discharged with no complications. Discussion Ossification of the abdominal incision wound due to surgical invasion was suspected, but it did not occur in the short term. Conclusion Two laparotomies could be performed safely in a patient with FOP.

Introduction The International Guidelines for Groin Hernia Management recommends an anterior repair after a failed posterior repair, and laparoscopic repair after a failed anterior tissue repair or Lichtenstein repair. However, there are not enough studies to guide decision-making for patients with recurrent hernia patients after combined anterior-posterior repair. We investigate the safety and usefulness of transabdominal preperitoneal repair (TAPP) for recurrent hernia patients after failed anterior-posterior repair. Methods We conducted a retrospective analysis of 13 consecutive patients with recurrent groin hernia who underwent TAPP after prior anterior preperitoneal mesh repair (that created anterior and posterior scarring) between September 2013 and October 2018. The control group comprised 45 patients who underwent TAPP for recurrent hernia after anterior repair (43 nonmesh repairs and two Lichtenstein repairs). Results There were no intraoperative complications, and chronic pain was not reported by the patients with prior anterior preperitoneal mesh repair. The mean operative time was 113 ± 31.3 minutes, and the mean postoperative stay was 1.62 ± 0.87 days. The Wong-Baker FACES rating scale score for pain on postoperative day 1 was 1.91 ± 1.5; on postoperative day 7, the score was 1.0 ± 0.89. None of these findings was significantly different from the findings in patients who had a prior anterior repair. A single patient experienced a further recurrence and underwent repeat TAPP. Conclusions The use of TAPP after failed combined anterior-posterior mesh repair may be feasible and safe for recurrent groin hernia. Further study is needed to determine long-term outcomes.

We report herein a patient with an inguinoscrotal hernia containing the urinary bladder. The hernia was safely repaired using the laparoscopic transabdominal preperitoneal repair technique. A 76-year-old man was admitted to our hospital with abdominal pain, vomiting, and diarrhea. His scrotum was swollen to fist size. Abdominal CT showed herniation of the sigmoid colon and the bladder into the right inguinal region, and his abdominal pain was attributed to incarceration of the sigmoid colon; this was manually reduced. About 1 month later, we performed transabdominal preperitoneal repair. After the direct hernial orifice was identified, the bladder was noted to be sliding from the medial side of the hernia; this was reduced. Peeling on the medial side was carried out to the middle of the abdominal wall, and the myopectineal orifice was covered with mesh. The patient was discharged on postoperative day 1.

Highlights • We must determine whether the plug or the onlay patch is the cause of chronic pain. • Laparoscopic plug removal for nociceptive pain due to a plug meshoma is effective. • We could avoid causing new-onset pain by not creating a groin incision., Introduction The use of tension-free mesh repair techniques for inguinal hernias has led to uniformly low recurrence rates. The main associated morbidity is chronic postoperative inguinal pain. Mesh removal and triple neurectomy is the indicated procedure; there is insufficient evidence to support mesh removal alone without neurectomy in patients with chronic postoperative inguinal pain. Presentation of case A 76-year-old man previously underwent repair of a right inguinal direct hernia using the plug-and-patch technique. Two years later, he experienced groin pain requiring the use of pain medication. Five years after surgery, he expressed the desire to remove the mesh because of chronic pain, rated 8 out of 10 on a numeric rating scale. We suspected that he was experiencing nociceptive pain caused by a plug meshoma, so we performed a laparoscopic plug extraction. His inguinal pain improved to 2 out of 10 on the second postoperative day, and he stopped taking pain medication by 10 months after surgery. Discussion The laparoscopic approach to plug removal is safe and simple. We successfully avoided causing new-onset pain by not using a groin incision to remove the mesh plug. Conclusion Laparoscopic plug removal for nociceptive pain due to a plug meshoma is effective. However, since there is insufficient evidence to recommend mesh removal without triple neurectomy, informed consent and further consideration of techniques and diagnostic methods are needed.

BACKGROUND The pathogenesis of delayed gastric emptying (DGE), a common complication of pancreaticoduodenectomy, is unclear. Loss of skeletal muscle mass (sarcopenia) is associated with post-pancreaticoduodenectomy complications; however, few studies have investigated the relationship between sarcopenia and DGE. The aim of this study was to investigate whether post-pancreaticoduodenectomy DGE is affected by pre-operative skeletal muscle mass. METHODS We retrospectively analysed the data of 112 consecutive patients who had undergone pancreaticoduodenectomy and divided them into the following two groups: no DGE (n = 100) and with DGE (n = 12). Patients were stratified by quartiles according to each element of body composition. The lowest quartile for skeletal muscle mass was defined as having sarcopenia. RESULTS Ten and two patients had grades B and C DGE, respectively. According to univariate analysis, body mass index (P = 0.031), clinically relevant post-operative pancreatic fistula (P

We report on a case of an infected urachal remnant successfully treated via a single-incisional laparoscopic technique. An 18-year-old woman was diagnosed with an infected urachal remnant. The center of the umbilicus was pulled and inverted from the skin, and the cephalic side of the urachus was dissected from the umbilicus. A single-incision laparoscopic technique employing ultrasonic coagulating shears was used to dissect the urachal remnant from the stump of the umbilicus to the caudal end. Single-incision laparoscopic excision of the urachal remnant can be used successfully as a minimally invasive technique with optimal cosmetic outcomes.

Primary duodenal adenocarcinoma is a rare disease, and cases with nodal metastases have a poor prognosis. A 46-year-old man complaining of bloody stool visited our hospital. Endoscopy, CT, and PET-CT showed adenocarcinoma in the 2nd portion of the duodenum. We performed radical resection (PpPD) and pathological findings showed T3N1M0 (Stage III). Chemotherapy consisting of FOLFOX6 was administered for 6 months after surgery. The patient was alive without recurrence 5 years later. This case suggests that adjuvant chemotherapy (FOLFOX regimen) following curative resection including lymph node removal is an effective treatment for cases with tumor involvement of the lymph nodes.

To clarify the molecular pathways governing hematopoietic stem cell (HSC) development, we screened a fetal liver (FL) HSC cDNA library and identified a unique gene, hematopoietic expressed mammalian polycomb ( hemp ), encoding a protein with a zinc-finger domain and four malignant brain tumor (mbt) repeats. To investigate its biological role, we generated mice lacking Hemp ( hemp −/− ). Hemp −/− mice exhibited a variety of skeletal malformations and died soon after birth. In the FL, hemp was preferentially expressed in the HSC and early progenitor cell fractions, and analyses of fetal hematopoiesis revealed that the number of FL mononuclear cells, including HSCs, was reduced markedly in hemp −/− embryos, especially during early development. In addition, colony-forming and competitive repopulation assays demonstrated that the proliferative and reconstitution abilities of hemp −/− FL HSCs were significantly impaired. Microarray analysis revealed alterations in the expression levels of several genes implicated in hematopoietic development and differentiation in hemp −/− FL HSCs. These results demonstrate that Hemp, an mbt-containing protein, plays essential roles in HSC function and skeletal formation. It is also hypothesized that Hemp might be involved in certain congenital diseases, such as Klippel-Feil anomaly.

症例は認知症を伴った86歳の男性で，75歳時に左鼠径ヘルニアに対し手術を受けていた．家族が左鼠径部膨隆に気付いたため，救急外来を受診した．腹部所見から左鼠径ヘルニアの嵌頓と診断したが，局所の発赤を認めなかったため，徒手的還納を行った．還納は容易であった．経過観察および待機手術目的で入院していたが，第3病日に腹部全体に筋性防御を認めたため腹部CTを行うと，腹水と小腸拡張像を認めた．急性腹膜炎と診断して開腹手術を行ったところ，S状結腸に壊死，穿孔を認めた．結腸穿孔部縫合閉鎖，ドレナージ，双孔式横行結腸人工肛門造設および腹腔内からのヘルニア門縫縮閉鎖術を施行し，救命した．徒手的還納後の結腸穿孔症例は極めてまれであるが，自覚症状が乏しい高齢者や認知症患者においては，嵌頓腸管が壊死に陥っているかの判断が困難であることもあり，徒手的還納の合併症の危険性を改めて認識すべきと考えられた．

再発鼠径ヘルニアに対する術式選択に関しては定まった見解が得られていないのが現状である．成人再発鼠径ヘルニア62例を検討し，再発手術の術式選択を考察した．62例中43例（69.3％）が内鼠径ヘルニア型の再発であった．再発までの期間はmesh plug法後が4.3±3.6年，Kugel法後が1.2±1.0年であり，tension-repair後の19.2±13.7年に比べ，有意に短かった．2005年までは後方よりの腹膜前腔アプローチで再発手術を多く行ったが，2006年以降はMillikan法が第一選択となった．鼠径管を再解放したにも関わらず，神経損傷による慢性疼痛や精索損傷をきたした症例はなかった．Millikan法は，再発形式として最も多い内鼠径ヘルニア型再発に対して手技が簡便であり，安全面においても問題ないことから，再発症例に対する術式としての有効性が示唆された．

p130Cas (Cas, Crk-associated substrate) is an adaptor molecule composed of a Src homology 3 (SH3) domain, a substrate domain (SD) and a Src binding domain (SBD). The SH3 domain of Cas associates with focal adhesion kinase (FAK), but its role in cellular function has not fully been understood. To address this issue, we established and analyzed primary fibroblasts derived from mice expressing a truncated Cas lacking exon 2, which encodes the SH3 domain (Cas Δexon 2). In comparison to wild-type cells, Cas exon 2Δ/Δ cells showed reduced motility, which could be due to impaired tyrosine-phosphorylation of FAK and Cas, reduced FAK/Cas/Src/CrkII binding, and also impaired localization of Cas Δexon 2 to focal adhesions on fibronectin. In addition, to analyze downstream signaling pathways regulated by Cas exon 2, we performed microarray analyses. Interestingly, we found that a deficiency of Cas exon 2 up-regulated expression of CXC Chemokine Receptor-4 and CC Chemokine Receptor-5, which may be regulated by IκBα phosphorylation. These results indicate that the SH3-encoding exon of Cas participates in cell motility, tyrosine-phosphorylation of FAK and Cas, FAK/Cas/Src/CrkII complex formation, recruitment of Cas to focal adhesions and regulation of cell motility-associated gene expression in primary fibroblasts.

Chronic myelogenous leukemia (CML) is a hematopoietic disorder, which begins as indolent chronic phase but inevitably progresses to fatal blast crisis. p210BCR/ABL, a constitutively active tyrosine kinase, is responsible for disease initiation but molecular mechanism(s) underlying disease evolution remains largely unknown. To explore this process, we employed retroviral insertional mutagenesis to CML-exhibiting p210BCR/ABL transgenic mice (Tg). Virus infection induced acute lymphoblastic leukemia (ALL) in p210BCR/ABL Tg with a higher frequency and in a shorter latency than wild-type littermates, and inverse PCR detected two retrovirus common integration sites (CISs) in p210BCR/ABL Tg tumors. Interestingly, one CIS was the transgene itself, where retrovirus integrations induced upregulation of p210BCR/ABL and production of truncated BCR/ABL with an enhanced kinase activity. Another CIS was Notch1 gene, where retrovirus integrations resulted in overexpression of Notch1 and generation of Notch1 lacking the C-terminal region (Notch1DeltaC) associated with stable expression of its activated product, C-terminal-truncated Notch intracellular domain (NICD Delta C). In addition, generation of Tg for both p210BCR/ABL and Notch1DeltaC developed ALL in a shortened period with Stat5 activation, demonstrating the cooperative oncogenicity of Notch1DeltaC/NICD Delta C with p210BCR/ABL involving Stat5-mediated pathway. These results demonstrated that overexpression/enhanced kinase activity of BCR/ABL and altered expression of Notch1 induces acute leukemia in a transgenic model for CML.

We report on a case of an infected urachal remnant successfully treated via a single-incisional laparoscopic technique. An 18-year-old woman was diagnosed with an infected urachal remnant. The center of the umbilicus was pulled and inverted from the skin, and the cephalic side of the urachus was dissected from the umbilicus. A single-incision laparoscopic technique employing ultrasonic coagulating shears was used to dissect the urachal remnant from the stump of the umbilicus to the caudal end. Single-incision laparoscopic excision of the urachal remnant can be used successfully as a minimally invasive technique with optimal cosmetic outcomes.

本邦では稀な疾患である原発性小腸軸捻転症の1例を経験し,腸切除せずに治癒しえたので報告する.症例は85歳,女性.開腹術の既往はない.腹痛と嘔吐のため受診し,腹部X線にてイレウスと診断され,入院となった.腹部CT検査で腸管拡張像と著明な腹水を認め,緊急手術を施行した.上腸間膜動脈根部付近で,小腸が時計周りに3回転捻転していた.誘因となる解剖学的異常はなく,原発性小腸軸捻転症と診断した.小腸壊死は認めず,軸捻転整復のみで手術を終了した.術後3日目より経口摂取を開始し,経過は良好であった.本症は術前診断が困難であるが,発症後,小腸が急激に壊死に陥ることが多い疾患である.開腹のタイミングを逸さないよう,特に所見に乏しいことが多い高齢者においては注意が必要である.

横行結腸原発の内分泌細胞癌の1例を経験した.症例は52歳,男性.左季肋部痛と発熱に対し,抗生剤を投与されるも軽快せず,当院紹介となった.腹部CTにて左上腹部に不整形腫瘤病変を認め,下部消化管内視鏡,注腸造影にて,横行結腸脾彎曲部寄りで管腔の著明な狭窄を認めた.横行結腸壁より発生した腫瘍であるとの診断にて,横行結腸切除術, 3群リンパ節郭清を行った.病理学的所見では,異型細胞が充実性の胞巣を形成しており,内分泌系のマーカーであるクロモグラニンAおよびLeu7 (CD57)が陽性であったことから内分泌細胞癌と診断した.内分泌細胞癌は急速に発育進展し,高率に転移する,生物学的にきわめて悪性度の高い腫瘍である.外科的治療のみでは根治は難しく,効果的な化学療法の検討が必要と思われる.

We have experienced a case of infection of an artificial vessel due to acute appendicitis in a 50-year-old man. The patent had undergone an abdominal arota-right femoral artery bypass operation using an artificial vessel in 1990. In 1995, he developed suppurative gonarthritis of the right lower limb, femoral osteomyelitis, and inflammation of the gastrocnemius and femoral muscles. These symptomas were improved by chemotherapy and incision drainage, though the etiology was unknown. In 1997, occlusion of the artificial vessel and suppurative lesions in the peripheral dorsal region of the foot and 3rd toe occurred, and a removal of the artificial vessel was conducted on November 8. On November 10, pus and intestinal juice like material flowed out from the wound. CT revealed gas in the retroperitoneal space, and a laparotomy was performed with a suspicion of perforation of the intestine. During operation the necrosed appendix, abscess formation and small bowel perforation were confirmed, and an appendectomy and a partial resection of the small intestine were carried out. Histologically, the appendix presented gangrenous appendicitis that might cause infection and occlusion of the artifical vessel. After the operation the inflammation was alleviated. There have been no signs of recurrence, and the patient is doing well.

Endometriosis is prevalent among women of reproductive age, and is most commonly found in the gynecologic organs themselves and the surrounding pelvic peritoneum. Endometriosis of the appendix, however, is rare. Preoperative diagnosis is difficult and a definitive diagnosis is usually established following histopathological examination of the appendix. We report a case of endometriosis of the appendix in a 29-year-old woman who presented with right lower quadrant abdominal pain. Rebound tenderness was localized to McBurney's point. Her WBC count was 12,300/mm3 and her CRP was 6.497 mg/dl. Ultrasound and computed tomography detected a calcified region inside the cecum and slight thickening of the wall of the appendix. Based on these findings, the patient was diagnosed with acute appendicitis and underwent an appendectomy. The appendix appeared mildly congested, but the mucosa of the appendix was nearly normal and without macroscopic inflammation. Histopathological examination demonstrated ectopic endometrial glands and stroma in the muscularis. These stroma cells were positive for CD10 on immunohistochemical staining, establishing a diagnosis of endometriosis of the appendix. The patient had a good clinical course and no residual pain postoperatively.

p130Cas, Crk-associated substrate (Cas), is an adaptor/scaffold protein that plays a central role in actin cytoskeletal reorganization. We previously showed that mice in which Cas was deleted (Cas(-/-)) died in utero because of early cardiovascular maldevelopment. To further investigate the in vivo roles of Cas, we generated mice with a hypomorphic Cas allele lacking the exon 2-derived region (Cas(Deltaex2/Deltaex2)), which encodes Src homology domain 3 (SH3) of Cas. Cas(Deltaex2/Deltaex2) mice again died as embryos, but they particularly showed progressive liver degeneration with hepatocyte apoptosis. Because Cas expression in the liver is preferentially detected in sinusoidal endothelial cells (SECs), the observed hepatocyte apoptosis was most likely ascribable to impaired function of SECs. To address this possibility, we stably introduced a Cas mutant lacking the SH3 domain (Cas DeltaSH3) into an SEC line (NP31). Intriguingly, the introduction of Cas DeltaSH3 induced a loss of fenestrae, the characteristic cell-penetrating pores in SECs that serve as a critical route for supplying oxygen and nutrients to hepatocytes. The disappearance of fenestrae in Cas DeltaSH3-expressing cells was associated with an attenuation of actin stress fiber formation, a marked reduction in tyrosine phosphorylation of Cas, and defective binding of Cas to CrkII.Cas plays pivotal roles in liver development through the reorganization of the actin cytoskeleton and formation of fenestrae in SECs.

心室中隔膜性部瘤と僧帽弁閉鎖不全症の希な合併症例に対して開心術を施行した. 症例は57歳, 男性. 平成5年に心臓カテーテル検査により心室中隔膜性部瘤および Sellers III度の僧帽弁閉鎖不全症と診断され, 以後, 外来で経過観察中であった. 平成10年になって労作時呼吸困難が出現し, 僧帽弁閉鎖不全症は Sellers IV度と悪化し, 同時に心室中隔膜性部瘤の増大も指摘された. 手術は, 瘤切除パッチ閉鎖術および僧帽弁形成術を施行した. 術後の心臓カテーテル検査で心室中隔膜性部瘤, 心室中隔欠損, 僧帽弁逆流を認めず, 術後25日目に退院した.

p130Cas (Cas, Crk-associated substrate) is an adaptor molecule composed of a Src homology 3 (SH3) domain, a substrate domain (SD) and a Src binding domain (SBD). The SH3 domain of Cas associates with focal adhesion kinase (FAK), but its role in cellular function has not fully been understood. To address this issue, we established and analyzed primary fibroblasts derived from mice expressing a truncated Cas lacking exon 2, which encodes the SH3 domain (Cas Deltaexon 2). In comparison to wild-type cells, Cas exon 2(Delta/Delta) cells showed reduced motility, which could be due to impaired tyrosine-phosphorylation of FAK and Cas, reduced FAK/Cas/Src/CrkII binding, and also impaired localization of Cas Deltaexon 2 to focal adhesions on fibronectin. In addition, to analyze downstream signaling pathways regulated by Cas exon 2, we performed microarray analyses. Interestingly, we found that a deficiency of Cas exon 2 up-regulated expression of CXC Chemokine Receptor-4 and CC Chemokine Receptor-5, which may be regulated by IkappaBalpha phosphorylation. These results indicate that the SH3-encoding exon of Cas participates in cell motility, tyrosine-phosphorylation of FAK and Cas, FAK/Cas/Src/CrkII complex formation, recruitment of Cas to focal adhesions and regulation of cell motility-associated gene expression in primary fibroblasts.

A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis (CRLM), which involved the right hepatic vein (RHV) and the inferior vena cava (IVC), was referred to our hospital. The metastatic lesion was diagnosed as initially unresectable because of its invasion into the confluence of the RHV and IVC. After she had undergone laparoscopic sigmoidectomy for the original tumor, she consequently had 3 courses of modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus cetuximab. Computed tomography revealed a partial response, and the confluence of the RHV and IVC got free from cancer invasion. After 3 additional courses of mFOLFOX6 plus cetuximab, preoperative percutaneous transhepatic portal vein embolization (PTPE) was performed to secure the future remnant liver volume. Finally, a right hemihepatectomy was performed. The postoperative course was uneventful. The patient was discharged from the hospital on postoperative day 13. She had neither local recurrence nor distant metastasis 18 mo after the last surgical intervention. This multidisciplinary strategy, consisting of conversion chemotherapy using FOLFOX plus cetuximab and PTPE, could contribute in facilitating curative hepatic resection for initially unresectable CRLM.