[A Case of Laparoscopic Repair for Hiatal Hernia Occurred Five Years after Esophagectomy for Esophageal Cancer].

A 70s man underwent minimally invasive esophagectomy and gastric conduit reconstruction via the posterior mediastinal route for early esophageal cancer 5 years ago. Three days prior to hospital visit, he presented with abdominal fullness, left chest pain, and vomiting. A CT revealed a postoperative hiatal hernia, and emergency surgery was performed laparoscopically. The laparoscopic findings showed that the transverse colon had prolapsed into the left thoracic cavity through the esophageal hiatus on the left side of the gastric conduit. The transverse colon had no sign of necrosis. The diaphragmatic defect was closed with unabsorbable suture. Increased bowel motility due to postoperative fat loss in the mesentery and intra-abdominal pressure are thought to be causes of the hernia. In addition, decreased adhesion formation due to endoscopic surgery may be a contributing factor. Although there is no unanimous opinion regarding the suture fixation of the conduit to the diaphragm after esophagectomy, it should be performed to prevent a herniation. Postoperative hiatal hernia occurs more than 5 years after the surgery is relatively rare, but its occurrence should be noted.

[A Case of Complete Response with S-1 plus Cisplatin Therapy Following Distal Gastrectomy for AFP-Producing Gastric Cancer with Liver Metastasis].

A 67-year-old man was admitted to our hospital because of nausea, anorexia and tarry stool. In the blood examination, serum α-fetoprotein(AFP)level was 1,650 ng/mL, and the upper gastrointestinal endoscopy showed a large hemorrhage tumor at the gastric body. Abdominal enhanced computed tomography(CT)showed a solitary mass in segment 4 of the liver. We performed distal gastrectomy, and administered S-1 plus cisplatin therapy. After 13 months, abdominal CT showed complete response for the metastatic tumor according to the Response Evaluation Criteria in Solid Tumors. Because of adverse events, S-1 monotherapy was administered from postoperative month 23. The patients survived for 66 months with no recurrence.

[A Case of Internal Hernia into a Reconstructed Pelvic Floor and Torsion of Jejunum near the Treitz Ligament after Laparoscopic Abdominoperineal Resection].

A 50s women underwent laparoscopic abdominoperineal resection(APR)for rectal cancer. Laparotomy was performed on the 8th postoperative day because of intestinal obstruction. An internal hernia was observed at the pelvic floor and the hernia orifice was found at the retroperitoneum that was sutured in the initial operation. On the other hand, the jejunum near the Treitz ligament was twisted, resulting in ischemic necrosis. The reason of the internal hernia is considered that a suction drain placed during the initial operation may have caused the rupture of the fragile part of the sutured peritoneum. Furthermore, increase of intra-abdominal pressure due to the internal hernia may have exacerbated the torsion of the jejunum near the Treitz ligament. This is probably due to the failure to the adequate reposition of the small intestine at the end of the initial operation. There is no consensus of the need for retroperitoneal sutures for APR. Currently, we only spray anti-adhesion agents on the pelvic floor without retroperitoneal reconstruction. Although the mobilization of small intestine is important to provide a good operative view in laparoscopic colorectal surgery, it is also important to confirm the reposition of the small intestine at the end of surgery.

[A Case of Intrahepatic Cholangiocarcinoma Confused with a Recurrent Hepatocellular Carcinoma Treated by RFA at Diagnosis].

Intrahepatic cholangiocarcinoma(ICC)is the second most common malignant liver tumor after hepatocellular carcinoma (HCC). ICC is usually ischemic; however, it has variable findings and may be difficult to differentiate from HCC. We report about a case of ICC that was difficult to distinguish from HCC treated by radiofrequency ablation(RFA). A 79‒year‒old woman underwent RFA for HCC of the caudate lobe. Two years after RFA, a spindle‒shaped tumor was identified near the previous treatment site using contrast‒enhanced MRI. Images showed posterior segment bile duct dilation, posterior segment atrophy of the liver parenchyma, and posterior segmental portal vein disruption. We performed surgery because of the suspicion of a recurrent HCC invading into the bile duct. Intraoperative findings showed posterior segment atrophy. Intraoperative echocardiography could not identify the tumor but revealed a tumor plug and portal vein disruption in the posterior segment. The patient underwent post‒enlargement segmentectomy, caudate lobectomy of the liver, and biliary neoplastic resection. Histopathological findings showed no malignant findings in the hepatocytes. A moderately differentiated adenocarcinoma was found in the expanded bile duct, which was diagnosed as an intrahepatic cholangiocarcinoma. Here, we report about the case along with a discussion and a bibliographical consideration.

Structural basis of Sec-independent membrane protein insertion by YidC.

Newly synthesized membrane proteins must be accurately inserted into the membrane, folded and assembled for proper functioning. The protein YidC inserts its substrates into the membrane, thereby facilitating membrane protein assembly in bacteria; the homologous proteins Oxa1 and Alb3 have the same function in mitochondria and chloroplasts, respectively. In the bacterial cytoplasmic membrane, YidC functions as an independent insertase and a membrane chaperone in cooperation with the translocon SecYEG. Here we present the crystal structure of YidC from Bacillus halodurans, at 2.4 Å resolution. The structure reveals a novel fold, in which five conserved transmembrane helices form a positively charged hydrophilic groove that is open towards both the lipid bilayer and the cytoplasm but closed on the extracellular side. Structure-based in vivo analyses reveal that a conserved arginine residue in the groove is important for the insertion of membrane proteins by YidC. We propose an insertion mechanism for single-spanning membrane proteins, in which the hydrophilic environment generated by the groove recruits the extracellular regions of substrates into the low-dielectric environment of the membrane.

[Gastric Complications in Stomach-Preserving Procedures on Total Pancreatectomy].

Whether the stomach should be preserved during total pancreatectomy(TP)is controversial. Therefore, we examined the correlation between stomach-preserving procedures on TP and postoperative gastric complications. Seven consecutive cases underwent TP(standard TP: 1 case, SSPTP: 3 cases, PPTP: 3 cases)for pancreatic cancer during the time period 2011-2019 at our hospital. There was no clinical case of postoperative gastric ulcer nor bleeding. Delayed gastric emptying(DGE)was observed in 4 cases of Grade A and 2 cases of Grade C. One of the Grade C cases was considered to be secondary DGE due to postoperative intestinal necrosis. The other was SSPTP case whose left gastric artery(LGA)was ligated. The patient had difficulty of food intake after the surgery and gastrointestinal endoscopy showed widespread hemorrhage and erosion of the gastric mucosa, considered to be ischemic gastropathy. Regarding primary DGE, most of cases were within Grade A even in stomach-preserving cases. Whereas, stomach-preserving procedure should be avoided when the LGA is ligated, because ischemic gastropathy may occur.

[A Rare Case of Gastric Metastasis from Cholangio Carcinoma].

An 80-year-old man was referred to our hospital because of jaundice and fatigue. Abdominal computed tomography(CT) scan revealed an extrahepatic bile duct tumor, and biliary cytology detected adenocarcinoma; therefore, subtotal stomachpreserving pancreaticoduodenectomy was performed. Histological analysis showed that the tumor was a well-differentiated adenocarcinoma without lymph node metastasis. Two years after the initial surgery, blood examination detected an elevated serum CA19-9 level and submucosal tumor which is 2.5 cm diameter with an ulcer at the gastrojejunostomy anastomosis. Tumor biopsy was performed, and histological analysis revealed a recurrent cholangiocarcinoma. The tumor directly invaded the transverse colon mesentery; therefore, distal gastrectomy and right hemicolectomy were performed. The patient survived 12 months postoperatively without recurrence. Gastric metastasis from cholangiocarcinoma rarely occurs. Intraoperative exposure of bile juice may have caused gastric metastasis in this case.

[A Case of Pancreatic Mixed Acinar-Neuroendocrine Carcinoma with Main Pancreatic Duct Development].

A 78-year-old man was referred to our hospital owing to a pancreatic tumor detected on ultrasonography. He showed weight loss, and his diabetes mellitus had worsened over 3 months. Abdominal contrast-enhanced computed tomography revealed a 3 cm diameter pancreatic head tumor with peripheral enhancement and a dilated pancreatic duct. He underwent subtotal stomach-preserving pancreaticoduodenectomy. Examination of intraoperative frozen sections did not indicate cancer involvement at the edge of the resected pancreatic duct. The tumor was histologically diagnosed as mixed acinar-neuroendocrine carcinoma(MANEC). It was mainly detected in the pancreatic head and was accompanied by intra-ductal growth in the pancreatic duct. The patient has survived for 21 months without recurrence. MANEC is a rare disease associated with intraductal growth. Intraoperative diagnosis of tumor involvement at the edge of the pancreatic duct may be useful for R0 resection in surgery for MANEC.

2.8-Å crystal structure of Escherichia coli YidC revealing all core regions, including flexible C2 loop.

YidC/Alb3/Oxa1 family proteins are involved in the insertion and assembly of membrane proteins. The core five transmembrane regions of YidC, which are conserved in the protein family, form a positively charged cavity open to the cytoplasmic side. The cavity plays an important role in membrane protein insertion. In all reported structural studies of YidC, the second cytoplasmic loop (C2 loop) was disordered, limiting the understanding of its role. Here, we determined the crystal structure of YidC including the C2 loop at 2.8 Šresolution with R/Rfree = 21.8/27.5. This structure and subsequent molecular dynamics simulation indicated that the intrinsic flexible C2 loop covered the positively charged cavity. This crystal structure provides the coordinates of the complete core region including the C2 loop, which is valuable for further analyses of YidC.

[A Radically-Resected Case of Ruptured IPMC of the Pancreas after Abscess Drainage Using an Endoscopic Naso-Pancreatic Drainage Tube].

A 79-year-old man was referred to our hospital because of sudden upper abdominal pain. Enhanced computed tomography revealed a huge multilocular cystic tumor with a thickened wall, which was connected with the main pancreatic duct of the pancreatic body. Abscess formation was seen inside the omental bursa; however, there were no signs of direct invasion of the cystic tumor into the stomach or transverse colon. Therefore, we performed emergency endoscopic naso-pancreatic drainage(ENPD)under the diagnosis of an intraperitoneal abscess caused by rupture of intraductal papillary mucinous carcinoma(IPMC). Four weeks later, distal pancreatectomy with omentectomy was performed to achieve curative resection of the ruptured IPMC. The postoperative course was uneventful and the patient was discharged on postoperative day 14. The pathological diagnosis was noninvasive IPMC. No signs of recurrence were seen until 12 months after surgery. Rupture of IPMC into the intraperitoneal space is rare; however, the prognosis is relatively poor because of the difficulty of curative resection. ENPD drainage before surgery is potentially useful for patients with ruptured IPMC to control local inflammation, which improves surgical curability.

Ultrasonic Cleaning for Irrigating Purulent Substances during Laparoscopic Gastrointestinal Surgery.

To improve the outcome of laparoscopic gastrointestinal surgery, improvement in the technology for removing purulent substances from the abdominal cavity is required. Ultrasonic cleaning technology may be suitable for the task. However, it is necessary to examine cleaning efficiency and safety through model tests that can lead to clinical trials for practical use. Nine surgical specialists first estimated the distribution of the actual attachment of purulent substances using videos of removing pus-like model dirt as an evaluation scale. Subsequently, cleaning tests were conducted using a small-size shower with model dirt that was somewhat difficult to remove, and its suitability as a model sample was confirmed. A mixture of miso and other substances was attached to a silicon sheet to prepare a test sample. The model dirt could be removed within a few seconds by cleaning using a probe-type ultrasonic homogenizer while the test sample was submerged in water. This performance greatly surpassed that of water flow cleaning under increased water pressure. An ultrasonic cleaner that is useful for irrigation during laparoscopic surgery will be suitable for practical use in laparoscopic surgery.

[A case of mediastinal lymph node metastasis from rectal cancer successfully treated by carbon ion radiotherapy].

We report a case of mediastinal lymph node metastasis from rectal cancer successfully treated by carbon ion radiotherapy. A 65-year-old woman underwent sigmoid colostomy against unresectable rectal cancer. After chemoradiotherapy, primary rectal cancer became resectable and low anterior resection was performed. Curative local resection was done and chemoradiotherapeutic effect was grade 2. Chemotherapy after the operation wasn't effective enough and the size of the mediastinal lymph node increased. So she underwent carbon ion radiotherapy (52.8 Gy) which markedly decreased the lymph node size (-48%). Multi-modality therapy, such as radiation, chemotherapy, operation and carbon ion radiotherapy was applied. Successfully, locally advanced rectal cancer was resected and distant lymph node metastasis was controllable.

Effect of immunonutrition on infectious complications in low skeletal muscle mass patients after pancreaticoduodenectomy.

BACKGROUND & AIMS: Sarcopenia is considered a risk factor of postoperative complications among patients undergoing abdominal surgery. However, few studies have demonstrated an effective strategy for reducing complications in sarcopenic patients. This study aimed to examine retrospectively the effect of preoperative immunonutrition on postoperative complications, especially infectious complications, in low skeletal muscle mass patients undergoing pancreaticoduodenectomy (PD). METHODS: This was a retrospective, consecutive cohort study conducted in our institution. Skeletal muscle mass was assessed using preoperative computed tomography images in 298 consecutive patients who underwent PD between May 2009 and May 2016. Cross-sectional areas at the third lumbar vertebrae normalized for stature (cm2/m2) were defined as the skeletal muscle mass index (SMI). Low SMI was defined as the lowest sex-specific quartile of SMI. Risk factors for postoperative infectious complications and the effect of preoperative immunonutrition on low SMI patients who underwent PD were evaluated. RESULTS: Results of multivariate analysis showed that the presence of low SMI and absence of preoperative immunonutrition were independent risk factors for postoperative infectious complications after PD (odds ratio [OR], 3.17 and 3.10, respectively; P < 0.001). In high SMI patients, the rate of postoperative infectious complications was significantly lower in those who received immunonutrition than in those who did not receive immunonutrition (31.9 vs. 46.1%, respectively; OR, 1.82; P = 0.045). Further, similar findings were exhibited in low SMI patients (26.3 vs. 83.6%, respectively; OR, 14.31; P < 0.001), even though OR was markedly higher in low vs. high SMI patients. CONCLUSION: There is a stronger association with reduced infectious complications in patients who have low SMI and receive immunonutrition (UMIN-CTR Identifier: UMIN000035775.).

[A case of lung metastases of colon cancer demonstrating complete response for more than five years after treatment with UFT].

A 77-year-old woman had a laparoscope assisted ileocecal resection for ascending colon cancer with multiple lung metastases in December 2003. The patient who had postoperative complication such as anastomotic leakage left the hospital in March 2004. UFT was administered from April 2004 to June 2006. One year after administration of UFT, CT showed the lung metastases had been disappeared and the level of CEA was decreased below normal. Recurrence was not observed for 62 months.

Remote Coupled Drastic ß-Barrel to ß-Sheet Transition of the Protein Translocation Motor.

The membrane protein SecDF, belonging to the RND superfamily, enhances protein translocation at the extracytoplasmic side using a proton gradient. Here, we report the crystal structure of SecDF in a form we named Super-membrane-facing (Super F) form, demonstrating a ß-barrel architecture instead of the previously reported ß-sheet structure. Through this structural insight and supporting results of an in vivo crosslinking experiment, we propose a remote coupling model in which a structural change of the transmembrane region drives a functional, extracytoplasmic conformational transition.

SecY-SecA fusion protein retains the ability to mediate protein transport.

In bacteria, the membrane protein complex SecY/E/G and SecA ATPase are essential for protein translocation. About 30% of newly synthesized proteins in the cytosol are targeted to and translocated across the cytoplasmic membrane by the Sec factors. Although a number of single-molecule analyses and structural studies, including the crystal structure of SecYEG complexed with SecA, have been published, the underlying molecular mechanisms and the functional oligomer states remain elusive. In this study, we constructed a fusion protein SecY-SecA, which induces the formation of the SecY-A/SecE/SecG complex (SecYAEG), to enable investigation of the molecular mechanisms by advanced single-molecule analyses. SecYAEG-reconstituted liposomes were found to possess protein translocation activity in vitro and form stable intermediates capable of the translocation using a mutant substrate protein. We additionally found that one unit of SecYAEG complex embedded into a nanodisc, using membrane scaffold proteins, interacts strongly with the substrate. The isolated SecYAEG-reconstituted nanodisc is a promising tool for investigation of the molecular mechanisms by which a single unit of Sec machinery mediates protein translocation.

Tunnel Formation Inferred from the I-Form Structures of the Proton-Driven Protein Secretion Motor SecDF.

Protein secretion mediated by SecYEG translocon and SecA ATPase is enhanced by membrane-embedded SecDF by using proton motive force. A previous structural study of SecDF indicated that it comprises 12 transmembrane helices that can conduct protons and three periplasmic domains, which form at least two characterized transition states, termed the F and I forms. We report the structures of full-length SecDF in I form at 2.6- to 2.8-Å resolution. The structures revealed that SecDF in I form can generate a tunnel that penetrates the transmembrane region and functions as a proton pathway regulated by a conserved Asp residue of the transmembrane region. In one crystal structure, periplasmic cavity interacts with a molecule, potentially polyethylene glycol, which may mimic a substrate peptide. This study provides structural insights into the Sec protein translocation that allows future analyses to develop a more detailed working model for SecDF.

Crystal Structures of SecYEG in Lipidic Cubic Phase Elucidate a Precise Resting and a Peptide-Bound State.

The bacterial SecYEG translocon functions as a conserved protein-conducting channel. Conformational transitions of SecYEG allow protein translocation across the membrane without perturbation of membrane permeability. Here, we report the crystal structures of intact SecYEG at 2.7-Å resolution and of peptide-bound SecYEG at 3.6-Å resolution. The higher-resolution structure revealed that the cytoplasmic loop of SecG covers the hourglass-shaped channel, which was confirmed to also occur in the membrane by disulfide bond formation analysis and molecular dynamics simulation. The cytoplasmic loop may be involved in protein translocation. In addition, the previously unknown peptide-bound crystal structure of SecYEG implies that interactions between the cytoplasmic side of SecY and signal peptides are related to lateral gate opening at the first step of protein translocation. These SecYEG structures therefore provide a number of structural insights into the Sec machinery for further study.

Crystal structure of Escherichia coli YidC, a membrane protein chaperone and insertase.

Bacterial YidC, an evolutionally conserved membrane protein, functions as a membrane protein chaperone in cooperation with the Sec translocon and as an independent insertase for membrane proteins. In Gram-negative bacteria, the transmembrane and periplasmic regions of YidC interact with the Sec proteins, forming a multi-protein complex for Sec-dependent membrane protein integration. Here, we report the crystal structure of full-length Escherichia coli YidC. The structure reveals that a hydrophilic groove, formed by five transmembrane helices, is a conserved structural feature of YidC, as compared to the previous YidC structure from Bacillus halodurans, which lacks a periplasmic domain. Structural mapping of the substrate- or Sec protein-contact sites suggested the importance of the groove for the YidC functions as a chaperone and an insertase, and provided structural insight into the multi-protein complex.