Thermostability and binding properties of single-chained Fv fragments derived from therapeutic antibodies.

Small antibody fragments have recently been used as alternatives to full-length monoclonal antibodies in therapeutic applications. One of the most popular fragment antibodies is single-chain fragment variables (scFvs), consisting of variable heavy (VH) and variable light (VL) domains linked by a flexible peptide linker. scFvs have small molecular sizes, which enables good tissue penetration and low immunogenicity. Despite these advantages, the use of scFvs, especially for therapeutic purpose, is still limited because of the difficulty to regulate the binding activity and conformational stability. In this study, we constructed and analyzed 10 scFv fragments derived from 10 representatives of FDA-approved mAbs to evaluate their physicochemical properties. Differential scanning calorimetry analysis showed that scFvs exhibited relatively high but varied thermostability, from 50 to 70°C of melting temperatures, and different unfolding cooperativity. Surface plasmon resonance analysis revealed that scFvs fragments that exhibit high stability and cooperative unfolding likely tend to maintain antigen binding. This study demonstrated the comprehensive physicochemical properties of scFvs derived from FDA-approved antibodies, providing insights into antibody design and development.

Evaluation of long-term chronic pain and outcomes for unilateral vs bilateral circular incision transabdominal preperitoneal inguinal hernia repair.

Aim: This study has two aims: to evaluate long-term chronic pain and complications after circular incision transabdominal preperitoneal inguinal hernia repair (C-TAPP) and compare outcomes of unilateral and bilateral inguinal hernia cases. Methods: A postoperative patient questionnaire was used to evaluate pain and complications in 1546 patients who underwent C-TAPP for simple inguinal hernia. Questions concerned satisfaction with surgery, pain at rest, pain at movement, mesh discomfort on a 10-point scale, and complications, such as recurrence. Patients were classified into unilateral (U Group) and bilateral (B Group) groups, and propensity score matching was performed to compare long-term chronic pain and complications. Results: The questionnaire return rates were 77.5% (1034 cases) and 79.9% (135 cases) in unilateral and bilateral cases. The frequency of moderate-to-severe (≥4 points) pain at rest, pain at movement, and mesh discomfort were 3.2%, 3.6%, and 4.5%, respectively. After propensity score matching, no significant differences in pain at rest (P = .726), at movement (P = .712), or mesh discomfort (P = .981) were detected between the U and B groups. Postoperative complications occurred in 2.1% of all patients, and the recurrence rate was 0.3%. In the post-match comparison, no differences in complications with Clavian-Dindo classification ≥III (U Group 0.7%, B Group 2.1%, P = .622) were detected. Conclusion: C-TAPP, which focuses on the layered structure, showed acceptable results for long-term chronic pain. Bilateral cases did not have worse pain or complications compared to unilateral cases.

Age, blood urea nitrogen, and lactate: Preoperative risk factors of laparotomy for strangulated small bowel obstruction.

INTRODUCTION: Despite increasing reports of laparoscopy for strangulated small bowel obstruction (SSBO), there is no consensus on outcomes in patients with SSBO. We evaluated the safety and utility of laparoscopy for SSBO and investigated the preoperative risk factors for laparotomy. METHODS: This retrospective study included 107 patients who underwent emergency surgery for SSBO over a period of 6 years. Patients' characteristics and surgical parameters were compared between 27 patients undergoing laparoscopy alone (group L) and 80 patients undergoing laparotomy (group O, including conversion). Univariate and multivariate analyses were performed to determine risk factors for laparotomy. RESULTS: Compared with group L, group O had significantly shorter operation time (59 vs 115 minutes, P < .001), shorter postoperative hospital stay (6 vs 10 days, P < .001), and fewer complications (3 vs 40 cases, P < .001). Age ≥ 68 years (odds ratio [OR] 3.970, P = .021), blood urea nitrogen (BUN) ≥ 14.6 mg/dL (OR 4.360, P = .012), and lactate ≥2.80 mmol/L (OR 12.90, P = .023) were independent risk factors for laparotomy. CONCLUSION: Prognosis was better in patients with SSBO undergoing complete laparoscopy than in patients undergoing laparotomy; however, age, BUN, and lactate were independent preoperative risk factors for laparotomy.

Simultaneous transabdominal preperitoneal hernia repair and laparoscopic cholecystectomy: A report of 17 cases.

INTRODUCTION: Inguinal hernia repair and cholecystectomy are frequently performed in the field of gastrointestinal surgery. However, reports describing surgical procedures that involve simultaneous transabdominal preperitoneal hernia repair (TAPP) and laparoscopic cholecystectomy (LC), as well as the safety and usefulness of this combination, are limited. Herein, we report a surgical procedure involving simultaneous TAPP and LC (TAPP + LC) and present the outcomes of patients who have undergone this combined surgical procedure, with a particular focus on its safety and usefulness. METHODS: We simultaneously performed TAPP + LC in 17 patients (mean age, 66.5 ± 8.1 years) with concomitant inguinal hernia and gallbladder stones. We assessed surgical outcomes. RESULTS: The mean operative time was 157 ± 39 min, and mean postoperative hospital stay was 3.2 ± 0.6 days. The median cost was $7673 for TAPP + LC. The mean postoperative length of hospital stay was 1.1 ± 0.6 day for TAPP alone and 3.4 ± 1.4 days for LC alone. The median costs of TAPP alone and LC alone were $4932 and $5453, respectively. Regarding intraoperative complications, the inferior epigastric vessels were damaged in two patients, and seroma was detected as a postoperative complication in one; these complications were spontaneously resolved. No mesh- or infection-related complications were noted. CONCLUSION: Simultaneous TAPP + LC is safe and can be regarded as a standard surgical procedure for patients with concomitant inguinal hernia and gallbladder stones. The TAPP + LC combination appears to help prevent the need for two hospitalizations and, thereby, reduces hospital stay and economic burden.

Sigmoid gallstone ileus: A case report and literature review in Japan.

INTRODUCTION: Gallstone as a cause of bowel obstruction is rare, and its occurrence in the colon is very infrequent. Here, we report the case of sigmoid gallstone ileus treated with one-stage operation. CASE PRESENTATION: A 65-year-old man visited our hospital because of abdominal pain and nausea. On the basis of the results of computed tomography, the patient was diagnosed with sigmoid gallstone ileus through cholecystocolonic fistula, and an emergency laparotomy was performed. Enterolithotomy, cholecystectomy, and fistula closure were performed in one-stage operation. Postoperatively, the patient developed biliary leakage, which rapidly recovered with conservative therapy. DISCUSSION AND CONCLUSION: The surgical treatment of gallstone ileus remains controversial. For postoperative infection control, one-stage operation can be considered for patients with gallstone ileus associated with cholecystocolonic fistula.

A rare case of secondary small bowel volvulus laparoscopically repositioned: literature review and classification.

BACKGROUND: Secondary small bowel volvulus is a rare condition caused by adhesions after laparotomy or tumors. There are no clear guidelines for indication of laparoscopic surgery. CASE PRESENTATION: A 69-year-old male visited our hospital complaining of epigastric pain. He had a history of hypopharyngeal carcinoma treated via pharyngolaryngoesophagectomy with restoration of esophageal continuity by harvesting a free jejunal autograft 6 years ago. Enhanced computed tomography revealed the whirl sign. An emergency laparoscopic operation was performed following a diagnosis of small bowel volvulus. This revealed rotation of the whole small bowel, involving the superior mesenteric artery as the center, and originating at the adhesion of the proximal and distal small bowel. Laparoscopic manipulation of volvulus and lysis of the adhesion were performed. The patient's postoperative course was uneventful, and he was discharged on hospital day 5. CONCLUSIONS: Laparoscopic surgery may be useful for treating small bowel volvulus; however, the patient's treatment indications should be judged carefully.

Two patients with spontaneous transomental hernia treated with laparoscopic surgery: a review.

Here, we report two patients with transomental hernia who were successfully treated with laparoscopic surgery. The first patient was a 58-year-old female who presented to our hospital with abdominal pain and vomiting; she had no history of abdominal surgery. Enhanced computed tomography revealed strangulation ileus due to an internal hernia. The second patient was a 36-year-old male who presented to our hospital with abdominal pain and no history of abdominal surgery. Enhanced computed tomography indicated transomental hernia. Emergency laparoscopic surgery in both patients revealed incarcerated bowel loops through defects in the greater omentum. The bowel segments were laparoscopically released, and the patients were uneventfully discharged on postoperative Days 4 and 8. Laparoscopic surgery is useful for the diagnosis and treatment of small bowel obstruction due to transomental hernia through the greater omentum.

Arteriovenous malformation in the sigmoid colon of a patient with Cowden disease treated with laparoscopy: a case report.

BACKGROUND: Cowden disease is a genetic disorder associated with a mutation of the PTEN gene and is known to be easily complicated by generalized vascular malformations and malignant tumors. However, only a few reports have investigated the relationship between Cowden disease and vascular malformations. We present a case of Cowden disease along with a review of the literature. CASE PRESENTATION: The patient was a 48-year-old man who visited our hospital complaining of fresh blood in his stools and shortness of breath. Hematological tests showed the patient had severe anemia. On physical examination, white papules-several millimeters in size-were observed between the patient's eyebrows. White papules were also observed on the left corner of his mouth and buccal mucosa. An upper gastrointestinal endoscopy showed densely-packed, white, flat protrusions in the esophagus. While lower gastrointestinal endoscopy revealed a mass accompanied by arterial pulsation in the sigmoid colon. A diagnosis of Cowden disease was confirmed and a laparoscopic sigmoidectomy was performed to address the arteriovenous malformations in the sigmoid colon. Post-surgery, the patient had an unremarkable recovery and was discharged 7 days later. CONCLUSIONS: We present a very rare case of Cowden disease with arteriovenous malformations occurring in the colon. Surgical resection is believed to be the first choice for treating congenital arteriovenous malformations of the intestines. However, the arteriovenous malformations in the colon in our patient were treated under laparoscopic guidance, making ours the first report describing laparoscopic treatment of colonic arteriovenous malformations occurring in the inferior mesenteric artery. Thus we demonstrate that laparoscopic treatment of arteriovenous malformations in the intestines is a minimally invasive and can be successfully applied in such cases.

Proper training in laparoscopic hernia repair is necessary to minimize the rising recurrence rate in Japan.

INTRODUCTION: The Japan Society for Endoscopic Surgery reported that the recurrence rate for inguinal hernia repair in Japan was less than 1% in 2010. However, its 2012 survey found that the recurrence rate had increased to 4% for the transabdominal preperitoneal procedure and 5% for the totally extraperitoneal procedure. We held 14 hernia repair training courses from 2011 to 2016 with help from Covidien. This study aimed to determine the effect of this training on the recurrence rate. METHODS: Training was composed of a theoretical revision of inguinal anatomy, dry laboratory suturing, a video lecture, and practice on an animal model. We made inquiries about the length of each surgeon's career, post-training changes in surgical methods, and recurrence rates before and after training. RESULTS: We received responses from 159 of 300 trainees (53%). The mean career length was 12.7 ± 8.2 years. The annual number of transabdominal preperitoneal procedures performed increased from 20.9 ± 29.9 to 32.4 ± 56.1 after training (P < 0.001), and the number of totally extraperitoneal procedures increased from 9.5 ± 13.9 to 13.9 ± 16.9 (P = 0.0218). The annual number of procedures performed via the anterior approach decreased from 153.1 ± 28.4 to 28.4 ± 52.2 after training (P < 0.001). The pre-training transabdominal preperitoneal procedure recurrence rate was 0.9%, and this decreased to 0.4% after training. There was no pre-training recurrence rate for the totally extraperitoneal procedure, but this was 0.4% after training. CONCLUSION: The high recurrence rate after inguinal hernia repair in Japan was mainly due to inadequate training in the laparoscopic method. Our laparoscopic hernia repair training course achieved low recurrence rates.

Laparoscopic-assisted total gastrectomy for early gastric cancer with situs inversus totalis: report of a first case.

BACKGROUND: Situs inversus totalis is a relatively rare condition and is an autosomal recessive congenital defect in which an abdominal and/or thoracic organ is positioned as a "mirror image" of the normal position in the sagittal plane. We report our experience of laparoscopic-assisted total gastrectomy with lymph node dissection performed for gastric cancer in a patient with situs inversus totalis. CASE PRESENTATION: A 58-year-old male was diagnosed with cT1bN0N0 gastric cancer. There were no vascular anomalies on abdominal angiographic computed tomography with three-dimensional reconstruction. laparoscopic-assisted total gastrectomy was performed with D1+ lymph node dissection, in accordance with the Japanese Gastric Cancer Treatment Guidelines. There were no intraoperative issues, and no postoperative complications. CONCLUSIONS: This was the first report describing laparoscopic-assisted total gastrectomy with the standard typical lymph node dissection in the English literature. We emphasize that the position of trocars and the standing side of the primary surgeon during the lymph node dissection are critical.

The overlap method is a safe and feasible for esophagojejunostomy after laparoscopic-assisted total gastrectomy.

BACKGROUND: Laparoscopic procedures are increasingly being applied to gastric cancer surgery, including total gastrectomy for tumors located in the upper gastric body. Even for expert surgeons, esophagojejunostomy after laparoscopy-assisted total gastrectomy (LATG) can be technically challenging. We perform the overlap method of esophagojejunostomy after LATG for gastric cancer. However, technical questions remain. Is the overlap method safer and more useful than other anastomosis techniques, such as methods using a circular stapler? In addition, while we perform this overlap reconstruction after LATG in a deep and narrow operative field, can the overlap method be performed safely regardless of body habitus? This study aimed to evaluate these issues retrospectively and to review the literature. METHODS: From October 2005 to August 2013, we performed LATG with lymph-node dissection and Roux-en-Y reconstruction using the overlap method in 77 patients with gastric cancer. This study examined pre-, intra- and postoperative data. RESULTS: Mean operation time, time to perform anastomosis, and estimated blood loss were 391.4 min, 36.3 min, and 146.9 ml, respectively. There were no deaths, and morbidity rate was 13%, including one patient (1%) who developed anastomotic stenosis. Mean postoperative hospitalization was 13.4 days. Surgical outcomes did not differ significantly by body mass index. CONCLUSIONS: First, the overlap method for esophagojejunostomy after LATG is safe and useful. Second, this method can be performed irrespective of the body type of the patient. In particular, in a deep and narrow operative field, the overlap method is more versatile than other anastomosis methods. We believe that the overlap method can become a standard reconstruction technique for esophagojejunostomy after LATG.

Evaluation of the delta-shaped anastomosis in laparoscopic distal gastrectomy: midterm results of a comparison with Roux-en-Y anastomosis.

BACKGROUND: Various methods of reconstruction after laparoscopic distal gastrectomy (LDG) have been developed and published, whereas only a limited number of reports are available on the utility of the delta-shaped anastomosis (Delta). This study compared Delta and Roux-en-Y anastomoses (RY), with the aim to clarify the utility of Delta. METHODS: Stage 1 gastric cancer patients who had undergone LDG with Delta (group D, n = 68) and those who had undergone LDG with RY (group RY, n = 60) were compared in terms of operative outcomes, postoperative clinical symptoms, gastrointestinal fiberscopic findings, and changes in body weight. RESULTS: Both the operative and anastomotic times were significantly shorter in group D (230 and 13 min, respectively) than in group RY (258 and 38 min, respectively) (p < 0.001). Among the complications observed at the anastomotic site, obstruction was seen in one group D patient and two group RY patients but was relieved with conservative management. Postoperative clinical symptoms were reported for 26.4% of the group D patients but had decreased to 5.9% 1 year later. Group RY yielded similar results. Upper gastrointestinal fiberscopy performed 1 year postoperatively showed no intergroup differences in the incidence of gastritis or residual retention and a significantly more frequent occurrence of bile reflux in group D. Postoperative weight changes did not differ between the two groups. CONCLUSIONS: Delta reconstruction after LDG is a safe and effective procedure that is totally laparoscopic, less time consuming, and associated with a favorable postoperative course and a better quality of life.

Rectal arteriovenous fistula resected laparoscopically after laparoscopic sigmoidectomy: a case report.

We report a very rare case of rectal arteriovenous fistula following sigmoidectomy and discuss this case in the context of the existing literature. In April 2011, the patient, a man in his 60s, underwent laparoscopic sigmoidectomy with lymph node dissection for sigmoid colon cancer. Beginning in February 2012, he experienced frequent diarrhea. Abdominal contrast-enhanced CT revealed local thickening of the rectal wall and rectal arteriovenous fistula near the anastomosis site. Rectitis from the rectal arteriovenous fistula was diagnosed. No improvement was seen with conservative treatment. Therefore, surgical resection was performed laparoscopically and the site of the lesion was confirmed by intraoperative angiography. The arteriovenous fistula was identified and resected. Postoperatively, diarrhea symptoms resolved, and improvement in rectal wall thickening was seen on abdominal CT. No recurrence has been seen as of 1 year postoperatively.

Establishment of a simple predictive scoring system for pancreatic fistula after laparoscopy-assisted gastrectomy.

BACKGROUND: The potential severity of postoperative pancreatic fistula (POPF) after laparoscopy-assisted gastrectomy (LAG) necessitates efforts to identify predictive factors for POPF. The aim of the present study was to identify predictive factors for POPF and to establish a predictive scoring system for POPF after LAG. PATIENTS AND METHODS: Between June 2004 and March 2011, 277 gastric cancer patients who underwent curative resection with LAG were enrolled. POPF was defined according to the International Study Group for Pancreatic Fistula grading system. Risk factors for POPF were evaluated using logistic regression analysis, and a scoring system for POPF was established. RESULTS: In the derivation cohort, multivariate analysis revealed the risk factors for POPF as patient age ≤70 years (5 points), amylase level of postoperative day 1 drainage fluid >454 IU/L(5 points), total number of retrieved lymph nodes >21 (5 points), body mass index >21.45 kg/m(2) (4 points), and operating time >337 min (2 points). In the validation cohort, at the cut-off point for high risk (score ≥15), the model had a negative predictive value of 94.5%, a positive predictive value of 57.4%, a sensitivity of 88.6%, and a specificity of 75.0% (C statistic = 0.857). CONCLUSION: This study demonstrated that POPF after LAG is associated with specific preoperative and postoperative factors. With a simple predictive scoring system, patients at high risk for POPF can be accurately identified. This simple predictive scoring system will be useful for many clinicians to assess the risk of POPF after LAG and start treating at-risk patients earlier.

[Prevention of oxaliplatin-related neurotoxicity by glutathione infusions].

We have used glutathione for prevention of oxaliplatin-related neurotoxicity with reference to the article of Cascinu et al. We investigated oxaliplatin-related neurotoxicity in Kariya Toyota General Hospital(KTGH)and compared with the data described in the article of Gamelin about the severity of its neurotoxicity. Grade 3 neurotoxicity was observed in only 5 of 44 patients(11.4%). The median number of cycles and cumulative dose of oxaliplatin were 12 cycles(5-27 / cycles)and 802.2(273.2-1,952.4)mg/m(2), respectively, at Grade 3 neuropathy. We evaluated retrospectively neuro-toxicity grade at cumulative oxaliplatin doses of approximately 500-520 mg/m(2). The severity of neurotoxicity observed in KTGH was significantly lower than in the group without Ca/Mg. We found no difference between the group with glutathione and / with Ca/Mg. Glutathione infusions seemed to prevent oxaliplatin-related neurotoxicity.

Gastrointestinal stromal tumor of the rectum with liver metastasis: report of a case.

Gastrointestinal stromal tumors (GISTs) have unique immunohistochemical and molecular genetic features that set them apart from leiomyomas, leiomyosarcomas, and schwannomas. Although recurrence of GIST usually tends to develop locally or in the liver, rectal GIST reoccur predominantly at the original site of the tumor. We describe a rare case of rectal GIST with multiple liver metastases. We carried out immunohistochemical staining for p53 protein, proliferating cell nuclear antigen (PCNA), integrins, and interleukin-1 receptor type I (IL-1RI) in order to investigate the degree of malignancy of this neoplasm in addition to the immunohistochemical analyses that were necessary for diagnosing GIST. Histologically, the rectal tumor was classified as an uncommitted type of rectal GIST with multiple liver metastases. Positive immunostaining for PCNA, alpha6 integrin subunit, and IL-1RI was found in both the rectal and hepatic tumors. The patients with a rectal GIST may have an increased risk of liver metastasis and a poor prognosis independent of the size of the tumor.

Laparoscopic surgery for diagnosis and treatment of bowel obstruction: case report of paracecal hernia.

BACKGROUND: Small bowel obstruction cased by paracecal hernia is rare, and the condition is difficult to diagnose preoperatively. We herein report a case of paracecal hernia that was successfully diagnosed and treated with laparoscopic surgery. CASE REPORT: A 74-year-old man admitted our hospital. His previous medical history included appendectomy and diabetes. He had abdominal distension with slight tenderness. Abdominal image examinations gave the appearance of a small bowel obstruction. An emergency operation was performed due to the fear of strangulation. We diagnosed the paracecal hernia with laparoscopy and treated it with a mini-laparotomy. After the operation he was discharged without complications. Using the laparoscopic technique we were able to undergo a minimally invasive treatment, and the patient continues to do well. CONCLUSIONS: This case suggests that the laparoscopic technique is useful for diagnosing and treatment of bowel obstructions.

Malignant solitary fibrous tumor originating from the peritoneum and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare neoplasm frequently involving the pleura. Benign and malignant forms of the tumor occur, the benign variant being three to four times more common than the malignant. CASE REPORT: We present herein a rare case of large malignant solitary fibrous tumor (SFT) originating from the peritoneum. An abdominal computed tomography scan revealed a well-defined solid tumor with mixed density. An abdominal ultrasonography (US) revealed a well-circumscribed solid tumor containing a partially cystic lesion. T1-weighted abdominal magnetic resonance imaging demonstrated a hypo- to isointensity, which was a hypo- to hyperintensity on T2-weighted images. Liposarcoma originating from the retroperitoneum was suggested, and the patient underwent a complete resection of the tumor as well as the left kidney because tumor invasion of the upper left kidney was suspected. Immunohistochemically, the spindle-shaped cells were positive for CD34, and the diagnosis was SFT originating from the peritoneum. At the 14-month follow-up evaluation, no recurrence or metastasis was detected. CONCLUSIONS: This case gave us some difficulty, and the correct diagnosis of the peritoneal mass was valuable. To diagnose the malignant potential of this type of tumor accurately may have value to direct the appropriate therapeutic operations after surgery and postoperative progress observation.

Clinicopathological and immunohistochemical analysis of malignant features in mucinous cystic tumors of the pancreas.

BACKGROUND/AIMS: To investigate the malignancy of mucinous cystic tumors (MCTs) of the pancreas, we examined clinicopathological features and immunohistochemical findings of MCT. METHODOLOGY: We analyzed the expression of p53 protein, proliferating cell nuclear antigen, alpha6-integrin subunit, alpha5beta1-integrin, and interleukin-1 receptor type I in tumor specimens from eight patients with MCT. RESULTS: The tumors were classified as mucinous cyst adenoma (n=6) or mucinous cyst adenocarcinoma (n=2). The actuarial five-year survival rate was 83.3%. All in eight MCTs had 'ovarian-type' stroma in the cyst wall. The alpha6-integrin subunit and p53 protein were expressed in adenocarcinoma tissues of MCTs, and in two adenomas the alpha6-integrin subunit and p53 protein were also co-expressed. CONCLUSIONS: Our present results indicate that coexpression of the alpha6-integrin subunit and p53 protein should be appreciated as an indicator of malignancy in MCTs.