Maternal impacts and perinatal outcomes after three types of bariatric surgery at a single institution.

PURPOSE: Bariatric surgery is widely known to improve pregnancy outcomes and to increase the risk of having small for gestational age neonates. However, the specific causes of neonatal growth restriction are still unclear. This study aimed to investigate the impacts of bariatric surgery on pregnancy and perinatal status at a single institution. METHODS: 24 women delivered singleton births among the 193 reproductive-aged women who underwent bariatric surgery. We classified the surgery into three types: laparoscopic adjustable gastric banding (LAGB; n = 6), laparoscopic sleeve gastrectomy (LSG; n = 5), and malabsorptive surgery (MS; n = 13), and investigated the pregnancy complications and perinatal impacts. RESULTS: The median maternal weight gain after LAGB was 12.5 kg (LSG 6.9 kg, MS 9.0 kg). Gestational hypertension was observed in half of the women who underwent LAGB, but in none of those who underwent MS. No significant difference in neonatal birth weight was observed between the LAGB (median 3272 g) and LSG (median 3005 g) groups. The maternal impact after MS was a remarkable decrease in hemoglobin during prepregnancy (median 1.9 g/dl). About 69% of women developed gestational anemia after MS, and their neonatal birth weight was the lowest (median 2660 g). However, the birth weight of neonates delivered by mothers without anemia after undergoing MS was similar to that of those delivered by mothers after undergoing other types of bariatric surgery (median 3037 g). CONCLUSIONS: Maternal anemia after MS may lead to low neonatal birth weight, which could be attributed to the large-scale reduction in maternal micronutrient levels.

Laparoscopic cholecystectomy and laparoscopic common bile duct exploration for cholecystolithiasis and choledocholithiasis in a patient with situs inversus totalis: A case report.

Situs inversus complicates diagnosis and treatment due to the mirrored organ placement in relation to normal anatomy. This report describes a 78-year-old female patient with situs inversus totalis who underwent laparoscopic cholecystectomy and laparoscopic common bile duct exploration for cholecystolithiasis and choledocholithiasis. Utilizing the "French mirror technique" for port placement, the surgeon adeptly mirrored standard maneuvers with a 2-mm needle forceps in the left hand and a 5-mm forceps in the right in a reversed anatomical setting. This technique maintained familiar hand movements, despite the patient's unique anatomy. The surgeon applied transcystic ductal bile duct exploration, using choledochoscopy for duct exploration and a basket catheter for stone removal. Laparoscopic cholecystectomy and common bile duct exploration through the transcystic ductal route are viable and effective for patients with situs inversus.

EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors.

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.).

Stenosis after use of the double-stapling technique for reconstruction after laparoscopy-assisted total gastrectomy.

BACKGROUND: The double-stapling technique (DST) for esophagojejunostomy using the transorally inserted anvil (OrVil; Covidien Japan, Tokyo, Japan) is one of the reconstruction methods used after laparoscopy-assisted total gastrectomy (LATG). This technique has potential advantages in terms of less invasive surgery without the need to create a complicated intraabdominal anastomosis. METHODS: From 2008 to 2011, 262 patients with gastric cancer underwent total gastrectomy and reconstruction with a Roux-en-Y anastomosis, and 52 patients underwent LATG with DST. A retrospective analysis then was performed comparing the patients who experienced postoperative stenosis after LATG-DST (positive group) and the patients who did not (negative group). A comparative analysis was performed among patients comparing conventional open total gastrectomy and LATG, and multivariate analysis was performed to evaluate risk factors for the development of anastomotic stenosis. RESULTS: A minor leak was found in 1 patient (1.9 %), and 11 patients experienced anastomotic stenosis (21 %) after LATG with DST. Among the patients with anastomotic stenosis, three (3/4, 75 %) anastomoses were performed with the 21-mm end-to-end anastomosis (EEA) stapler, and eight anastomoses were performed (8/47, 17 %) with the 25-mm EEA stapler. The median interval to the diagnosis of anastomotic stenosis was 43 days after surgery. The patients with stenosis needed endoscopic balloon dilation an average of four times, and the rate of perforation after dilation was 13 %. The clinical and operative characteristics did not differ between the two groups. Anastomotic stenosis after open total gastrectomy occurred in two cases (0.98 %). Multivariate analysis showed that the size of the EEA stapler and the use of DST were risk factors for anastomotic stenosis. CONCLUSION: Esophagojejunostomy using DST with OrVil is useful in performing a minimally invasive procedure but carries a high risk of anastomotic stenosis.

Oncogenic MAP2K1 mutations in human epithelial tumors.

The scirrhous subtype of gastric cancer is a highly infiltrative tumor with a poor outcome. To identify a transforming gene in this intractable disorder, we constructed a retroviral complementary DNA (cDNA) expression library from a cell line (OCUM-1) of scirrhous gastric cancer. A focus formation assay with the library and mouse 3T3 fibroblasts led to the discovery of a transforming cDNA, encoding for MAP2K1 with a glutamine-to-proline substitution at amino acid position 56. Interestingly, treatment with a MAP2K1-specific inhibitor clearly induced cell death of OCUM-1 but not of other two cells lines of scirrhous gastric cancer that do not carry MAP2K1 mutations, revealing the essential role of MAP2K1(Q56P) in the transformation mechanism of OCUM-1 cells. By using a next-generation sequencer, we further conducted deep sequencing of the MAP2K1 cDNA among 171 human cancer specimens or cell lines, resulting in the identification of one known (D67N) and four novel (R47Q, R49L, I204T and P306H) mutations within MAP2K1. The latter four changes were further shown to confer transforming potential to MAP2K1. In our experiments, a total of six (3.5%) activating mutations in MAP2K1 were thus identified among 172 of specimens or cell lines for human epithelial tumors. Given the addiction of cancer cells to the elevated MAP2K1 activity for proliferation, human cancers with such MAP2K1 mutations are suitable targets for the treatment with MAP2K1 inhibitors.

Intraoperative holography navigation using a mixed-reality wearable computer during laparoscopic cholecystectomy.

BACKGROUND: Mixed-reality technology, a new digital holographic image technology, is used to present 3-dimensional (3D) images in the surgical space using a wearable mixed-reality device. This study aimed to assess the safety and efficacy of laparoscopic cholecystectomy using a holography-guided navigation system as an intraoperative support image.In this prospective observational study, 27 patients with cholelithiasis or mild cholecystitis underwent laparoscopic cholecystectomy between April 2020 and November 2020. Nine patients underwent laparoscopic cholecystectomy with 3D models generated by a wearable mixed-reality device (laparoscopic cholecystectomy with 3D models) and 18 underwent laparoscopic cholecystectomy with conventional two-dimensional images (laparoscopic cholecystectomy with 2D images) as surgical support images. Surgical outcomes such as operative time, blood loss, and perioperative complication rate were measured, and a four-item questionnaire was used for subjective assessment. All surgeries were performed by a mid-career and an experienced surgeon. RESULTS: Median operative times of laparoscopic cholecystectomy with 3-dimensional models and 2-dimensional images were 74.0 and 58.0 minutes, respectively. No intraoperative blood loss or perioperative complications occurred. Although the midcareer surgeon indicated that laparoscopic cholecystectomy with 3-dimensional models was "normal" or "easy" compared with 2-dimensional images in all cases, the experienced surgeon rated 3-dimensional models as more difficult in 3 (33%) of 9 cases. CONCLUSION: This study provides evidence that laparoscopic cholecystectomy with 3-dimensional models is feasible. However, the efficacy of laparoscopic cholecystectomy with 3-dimensional models may depend on the surgeon's experience, as indicated by the different ratings provided by the surgeons.

Application of a novel surgical difficulty grading system during laparoscopic cholecystectomy.

BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2  = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.

Internal hernia after laparoscopic gastric resection with antecolic Roux-en-Y reconstruction for gastric cancer.

BACKGROUND: To decrease the incidence of internal hernia after laparoscopic gastric bypass, current recommendations include closure of mesenteric defects. Laparoscopic gastric resection is used increasingly for the treatment of gastric cancer, but the incidence of internal hernia in the treated patients has not been studied. METHODS: This study retrospectively reviewed 173 patients who underwent laparoscopic resection for gastric cancer at one institution, including distal and total gastric resections with antecolic Roux-en-Y reconstruction. RESULTS: An internal hernia occurred in 4 (7%) of 58 patients whose jejunojejunal mesenteric defect was not closed a mean of 326 days after surgery. All the patients underwent reoperation with reduction and repair of the hernia. In 115 subsequent cases, with closure of the mesenteric defect, internal hernias did not occur (0/115 cases; p < 0.05). CONCLUSION: Based on the current recommendations for patients undergoing bariatric surgery, closure of this potential hernia defect is mandatory after laparoscopic gastrectomy with a Roux-en-Y reconstruction for gastric cancer.

A mouse model for EML4-ALK-positive lung cancer.

EML4-ALK is a fusion-type protein tyrosine kinase that is generated in human non-small-cell lung cancer (NSCLC) as a result of a recurrent chromosome inversion, inv (2)(p21p23). Although mouse 3T3 fibroblasts expressing human EML4-ALK form transformed foci in culture and s.c. tumors in nude mice, it has remained unclear whether this fusion protein plays an essential role in the carcinogenesis of NSCLC. To address this issue, we have now established transgenic mouse lines that express EML4-ALK specifically in lung alveolar epithelial cells. All of the transgenic mice examined developed hundreds of adenocarcinoma nodules in both lungs within a few weeks after birth, confirming the potent oncogenic activity of the fusion kinase. Although such tumors underwent progressive enlargement in control animals, oral administration of a small-molecule inhibitor of the kinase activity of ALK resulted in their rapid disappearance. Similarly, whereas i.v. injection of 3T3 cells expressing EML4-ALK induced lethal respiratory failure in recipient nude mice, administration of the ALK inhibitor effectively cleared the tumor burden and improved the survival of such animals. These data together reinforce the pivotal role of EML4-ALK in the pathogenesis of NSCLC in humans, and they provide experimental support for the treatment of this intractable cancer with ALK inhibitors.

Identification of the transforming activity of Indian hedgehog by retroviral expression screening.

To identify novel cancer-promoting genes in biliary tract cancer (BTC), we constructed a retroviral cDNA expression library from a clinical specimen of BTC with anomalous pancreaticobiliary duct junction (APBDJ), and used the library for a focus formation assay with 3T3 fibroblasts. One of the cDNAs rescued from transformed foci was found to encode Indian hedgehog homolog (IHH). The oncogenic potential of IHH was confirmed both in vitro with the focus formation assay and in vivo with a tumorigenicity assay in nude mice. The isolated IHH cDNA had no sequence alterations, suggesting that upregulation of IHH expression may contribute to malignant transformation. Quantitation of IHH mRNA among clinical specimens has revealed that the expression level of IHH in BTC with APBDJ is higher than that in BTC without APBDJ and than in non-cancerous biliary tissues. Our data thus implicate a direct role of IHH in the carcinogenesis of BTC with APBDJ.

Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening.

Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract.

Alternate-day treatment with S-1 in patients with gastric cancer: a retrospective study of strategies for reducing toxicity.

BACKGROUND: In patients with adverse events of S-1, the dose is generally reduced or the treatment cycle is shortened. Whether the therapeutic effectiveness of modified regimens is similar to that of the standard dosage remains unclear. METHODS: We retrospectively studied patients with gastric cancer who received S-1 on alternate days. RESULTS: A total of 266 patients received S-1 on alternate days. In 116 patients, S-1 was initially given at the standard dosage but was switched to alternate-day treatment because of toxicity within 28 days on average. The other 150 patients initially received alternate-day treatment because of poor general condition. In the adjuvant chemotherapy group (n = 96), the 3-year survival rate was 88% in patients with stage II, 73% in stage IIIA, and 67% in stage IIIB who underwent D2 lymph-node dissection. In the palliative surgery group (n = 96), the response rate was 13%, with a median survival time (MST) of 624 days. In patients with unresectable/recurrent disease (n = 74), the response rate was 25%, with an MST of 338 days. Among the 116 patients who initially received treatment on consecutive days, 100% had grade 1, 53% had grade 2, and 5.2% had grade 3 adverse events. When S-1 was switched to alternate-day treatment, toxicity decreased in all patients. In the 266 patients who received alternate-day treatment, 8% had grade 1, 6% had grade 2, and 0% had grade 3 adverse events. CONCLUSION: Alternate-day treatment with S-1 may have milder adverse events without compromising therapeutic effectiveness.

Preoperative diagnosis of a gastric extremely well-differentiated adenocarcinoma: A case report.

INTRODUCTION: Gastric adenocarcinomas with low grade atypia may be difficult to diagnose as gastric cancer by preoperative biopsy. We report an extremely well-differentiated adenocarcinoma (EWDA) of the stomach which appeared like a submucosal tumor diagnosed by preoperative endoscopic submucosal dissection. PRESENTATION OF CASE: A 70-year-old male was referred with a 3-month history of a submucosal-appearing lesion in the gastric wall found on endoscopy. Biopsies of the lesion were performed and were inconclusive for neoplasia. Endoscopic ultrasonography showed a low echoic tumor growing into the fourth layer of the gastric wall. It was difficult to identify the tumor by repeat biopsy. Endoscopic submucosal dissection of the lesion was performed and revealed adenocarcinoma, and laparoscopic total gastrectomy was performed. Histopathologic evaluation showed that the tumor was stage IIA (T3N0M0). There is no recurrence 12 months after resection. DISCUSSION: Gastric EWDAs are rare lesions, accounting for 0.6% of all gastric cancers. It is difficult to diagnose gastric EWDA especially if it appears like a submucosal tumor. This lesion was finally diagnosed by endoscopic submucosal dissection. CONCLUSION: Endoscopic submucosal dissection may facilitate establishing the preoperative diagnosis of a tumor thought to be a gastric EWDA based on its endoscopic appearance and pathological findings.

Pathological complete response after intraperitoneal paclitaxel and systemic combined chemotherapy in a patient with peritoneal metastases from gastric cancer: a case report.

BACKGROUND: Despite recent progress in systemic chemotherapy, the prognosis of patients with peritoneal metastases from gastric cancer is still poor. Efficacious intraperitoneal and systemic combination chemotherapy regimens to treat patients with peritoneal metastases have recently been developed. CASE PRESENTATION: A 74-year-old man with gastric cancer T4b (transverse mesocolon) N3 M1 (peritoneum) received combination chemotherapy with intraperitoneal administration of paclitaxel, intravenous oxaliplatin, and oral S-1. Eight courses of combined chemotherapy had remarkable anti-tumor effects on the primary lesion, lymph node metastases, and peritoneal metastases. Total gastrectomy with regional lymph node dissection was performed. Pathological examination revealed no viable tumor cells in the resected specimens. After gastrectomy, the patient received 25 courses of the same chemotherapy without oxaliplatin and has no evidence of recurrence 24 months later. DISCUSSION: Therapeutic approaches including systemic chemotherapy, extended resection, and heated intraperitoneal chemotherapy have been used to treat patients with peritoneal metastases. Repeat therapy with intraperitoneal paclitaxel has been used recently. Intraperitoneal administration of paclitaxel results in prolonged retention in the peritoneal cavity with effects against peritoneal metastases. Repeated administration of paclitaxel does not cause adhesions in the peritoneal cavity. When combination chemotherapy is effective, salvage gastrectomy is a promising option with minimal morbidity and mortality. CONCLUSION: Combined chemotherapy with intraperitoneal paclitaxel and systemic chemotherapy followed by gastrectomy is a promising strategy for patients with advanced gastric cancer and peritoneal metastases.

Gasless laparoscopic distal gastrectomy with Roux-en-Y reconstruction.

BACKGROUND/AIMS: Laparoscopic-assisted distal gastrectomy (LADG) is a minimally invasive procedure for patients with gastric carcinoma. We have previously reported gasless LADG with a Billroth-I reconstruction using a 5-7cm minilaparotomy. We modified the technique for gasless LADG to include a Roux-en Y reconstruction and to expand the indications for its use. METHODOLOGY: A total of 40 patients with early stage gastric tumors (T1 n=38, T2 n=2) underwent this procedure. Following gasless laparoscopic distal gastrectomy with lymph node dissection, a jejunum to greater curvature of the gastric remnant anastomosis was performed using an intracorporeal laparoscopic stapled method. The jejuno-jejunal anastomosis was performed using a hand-sewn technique under direct vision through a mini-laparotomy. RESULTS: The mean surgical time (n=40) was 222 min, estimated blood loss 101 ml, and the mean number of lymph nodes harvested was 21. There were no postoperative complications such as bleeding, leak, or cardio-pulmonary dysfunction. Mean body weight loss was 3.9 kg, and there is no evidence of recurrence during a mean followup of 14 months. CONCLUSIONS: Gasless LADG with Roux-en-Y reconstruction is a feasible, novel procedure for a minimally invasive approach to gastric cancer.

Correction to: Preoperative Weight Loss and Operative Outcome After Laparoscopic Sleeve Gastrectomy.

In Table 2 on p. 2517 the heading for Group 3 should read as follows.

Non-exposed endoscopic wall-inversion surgery for pediatric gastrointestinal stromal tumor: A case report.

Gastrointestinal stromal tumors (GIST) in patients under 18 years of age are classified as pediatric GIST. Pediatric GIST are extremely rare, and there are no reports of laparoscopic-endoscopic cooperative surgery for these lesions. We report the use of non-exposed endoscopic wall-inversion surgery as a laparoscopic-endoscopic cooperative surgery-related procedure for the treatment of a pediatric GIST. The case involved a 17-year-old male patient who presented with anemia and was found to have a bleeding gastric tumor. The tumor was resected transorally using the non-exposed endoscopic wall-inversion surgery technique. No gene mutation of c-Kit or Platelet-Derived Growth Factor Receptor α (PDGFRα) was found, and the final pathological diagnosis was epithelial-type GIST due to a succinate dehydrogenase abnormality. Follow-up included a CT scan every 4 months. No recurrence has occurred to date.

Combined subtotal gastrectomy and splenectomy after partial splenic embolization for a patient with gastric cancer and immune thrombocytopenic purpura: A case report.

INTRODUCTION: Immune thrombocytopenic purpura is an acquired thrombocytopenia. Preoperative management of thrombocytopenia is important in patients with gastric cancer. Partial splenic embolization can be effective for patients with thrombocytopenia, but could lead to ischemic necrosis of the remnant stomach when performing subtotal gastrectomy with splenectomy. PRESENTATION OF CASE: The patient is an 84-year old woman evaluated for anemia. Endoscopy revealed an advanced gastric cancer with bleeding. The patient also had immune thrombocytopenic purpura with a platelet count <50,000/µL. Administration of platelets did not increase the platelet count. Partial splenic embolization was performed followed by administration of high-dose immunoglobulin. The platelet count was over 50,000/µL preoperatively. The patient underwent combined subtotal gastrectomy and splenectomy, followed by an uneventful course. DISCUSSION: Patients with immune thrombocytopenic purpura and advanced gastric cancer can have anemia. Partial splenic embolization has been used to treat patients with refractory immune thrombocytopenic purpura as an alternative to splenectomy. Preoperative partial splenic embolization and high-dose immunoglobulin therapy resulted an increased platelet count in this patient. Elderly patients with gastric cancer have a high risk of postoperative complications. Patients with gastric cancer undergoing total gastrectomy have an impaired postoperative quality of life compared to those who undergo subtotal gastrectomy. We performed a subtotal gastrectomy and splenectomy as a function-preserving operation, completed safely by maintaining blood flow to the remnant stomach. CONCLUSION: Partial splenic embolization is effective for patients with immune thrombocytopenic purpura and gastric cancer. Combined subtotal gastrectomy and splenectomy is achieved by preserving blood flow to the remnant stomach.