Long-Term Complete Response to Trastuzumab Deruxtecan in a Case of Unresectable Gastric Cancer.

Introduction: Trastuzumab deruxtecan (T-Dxd) has been approved for the treatment of HER2-positive gastric cancer. However, there are only a limited number of cases of gastric cancer where a long-term complete response (CR) has been maintained. Consequently, we report a case of gastric cancer in which long-term CR was maintained. Case Presentation: A woman in her late 60s underwent a gastrointestinal endoscopy, which revealed a type 2 lesion with ulceration in the lesser curvature of the vestibule, and a biopsy, which revealed an adenocarcinoma. Computed tomography (CT) revealed wall thickening of the gastric antecubital region, metastatic liver tumor, and extra-regional lymph node metastasis; a diagnosis of T4a, N3a, M1 (H, LYN), and cStage IVB (HER2 3+) was confirmed. Trastuzumab, oxaliplatin, and S-1 were administered initially. After 9 months, ascites appeared, and progressive disease was diagnosed. Paclitaxel and ramucirumab were started as second-line treatments but discontinued owing to neutropenia and increasing ascites. Third-line treatment with T-Dxd was initiated, and 11 months later, CT showed the disappearance of metastases. Even after 31 months, the CR was maintained. Conclusion: To the best of our knowledge, this is one of the few cases in which long-term CR was maintained with third-line T-Dxd treatment. Treatment strategies for patients with gastric cancer to achieve long-term CR require careful consideration.

A rare case of multiple port site incisional hernias repaired by laparoscopy-assisted intraperitoneal onlay mesh: A case report.

INTRODUCTION: Port site herniation is a frequent complication of abdominal surgery, yet treatment strategies for multiple port site hernias are often difficult and case reports are rare. PRESENTATION OF CASE: A 72-year-old woman, with a history of multiple abdominal surgeries, underwent laparoscopic surgery for rectal prolapse four years prior. Three 12 mm ports were inserted into the umbilical region, right upper quadrant and right lower abdomen, subsequently, incisional hernias developed at all three sites. In addition, an incisional hernia developed in the lower abdomen, for a total of four incisional hernias. She was taking apixaban for atrial fibrillation, and since the standard surgical method of placing the mesh in the extraperitoneal space was judged to be high risk for postoperative bleeding and hematoma formation, we performed a laparoscopy-assisted intraperitoneal onlay mesh repair (IPOM). DISCUSSION: The key points of the surgery performed are: Laparoscopic surgery was initiated with a small incision in the umbilical region, using two 5 mm ports because we reasoned that using a 12 mm port could cause a new hernia. In the lateral hernia repair, a mesh was placed in the preperitoneal space on the dorsal side of the hernia, the mesh was sutured to the peritoneum because tucking cannot be performed if nerves are present on the dorsal aspect. The medial hernia was repaired by IPOM via a small laparotomy incision. CONCLUSION: For multiple incisional hernias, it is necessary to consider appropriate repair methods for each site.

Surgical strategies for localized colorectal amyloidosis.

BACKGROUND: Localized colorectal amyloidosis has a good prognosis, but cases involving bleeding or perforation may require surgery. However, there are few case reports discussing the differences in the surgical strategy between the segmental and pan-colon types. CASE PRESENTATION: A 69-year-old woman with a history of abdominal pain and melena was diagnosed with amyloidosis localized in the sigmoid colon by colonoscopy. Since preoperative imaging and intraoperative findings could not rule out malignancy, we performed laparoscopic sigmoid colectomy with lymph-node dissection. Histopathological examination and immunohistochemical staining revealed a diagnosis of AL amyloidosis (λ type). We diagnosed localized segmental gastrointestinal amyloidosis, because there was no amyloid protein in the margins, and the tumor was localized. There were no malignant findings. CONCLUSIONS: Unlike systemic amyloidosis, localized amyloidosis has a favorable prognosis. Localized colorectal amyloidosis can be classified into the segmental type, in which amyloid protein is deposited locally, and the pan-colon type, in which amyloid protein is deposited extensively in the colon. Amyloid protein causes ischemia due to vascular deposition, weakening of the intestinal wall due to muscle layer deposition, and decreased peristalsis due to nerve plexus deposition. No amyloid protein should remain outside the resection area. The pan-colon type is often reported to cause complications such as anastomotic leakage, and primary anastomosis should be avoided. On the other hand, if there is no contamination or tumor remnants in the margin, the segmental type may be considered for primary anastomosis.

Gastric volvulus associated with shrinkage of a gastrointestinal stromal tumor by neoadjuvant imatinib: a case report.

BACKGROUND: During neoadjuvant chemotherapy for giant gastrointestinal stromal tumors, changes in gastrointestinal stromal tumor size are rarely associated with events such as perforation and bleeding that require emergency surgery. Moreover, it is very rare for gastrointestinal stromal tumors to shrink and become mobile, resulting in gastric volvulus. Herein, we report a case of gastrointestinal stromal tumor shrinkage during neoadjuvant imatinib treatment, resulting in gastric volvulus that required surgery. To the best of our knowledge, this is the first reported occurrence of gastric volvulus during neoadjuvant imatinib treatment for a giant gastrointestinal stromal tumor. CASE PRESENTATION: A 58-year-old Japanese woman who was diagnosed with a giant gastric gastrointestinal stromal tumor and administered neoadjuvant imatinib presented to our hospital with complaints of abdominal pain and retching. Enhanced computed tomography revealed that the gastrointestinal stromal tumor had shrunk and shifted in position, and the stomach had organoaxially twisted. Accordingly, the patient was diagnosed with gastric volvulus caused by a gastric gastrointestinal stromal tumor. Conservative treatment did not improve the volvulus; hence, laparotomy was performed. The tumor developed from the lesser curvature of the stomach and caused rotation of the gastric body. The local gastric wall was resected. Histopathological examination confirmed the diagnosis of gastrointestinal stromal tumor. The patient received adjuvant imatinib for 3 years and has been alive for 5 years without recurrence. CONCLUSIONS: Gastric volvulus can be caused by the laxity of the ligaments that hold the stomach and gastric ptosis or esophageal hernia and diaphragmatic hernia; therefore, gastric gastrointestinal stromal tumors rarely cause gastric volvulus. However, a risk of torsion exists if the gastrointestinal stromal tumor develops extramural to lesser curvature and attains a certain size.

Current treatment strategies and future perspectives for gastrointestinal stromal tumors.

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.

Laparoscopic transabdominal preperitoneal repair for recurrent groin hernia after failed anterior-posterior repair.

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.

Laparoscopy-assisted repair with Ventralex ST Hernia Patch for a small subcostal hernia: A case report.

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.

Solitary peritoneal metastasis of gastrointestinal stromal tumor: A case report.

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.

Fibrodysplasia ossificans progressiva with two emergency laparotomies: A case report.

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.

Laparoscopic plug removal for chronic pain after inguinal hernia repair using the plug-and-patch technique: A case report.

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.

Sarcopenia is an independent predictor of delayed gastric emptying following pancreaticoduodenectomy: a retrospective study.

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 < 0.001) and skeletal muscle mass (P = 0.002) were significantly associated with DGE. According to multivariate analysis, high body mass index (≥25 kg/cm2 ) (P = 0.005), post-operative pancreatic fistula (P = 0.027) and low skeletal muscle mass (P = 0.004) were independently associated with DGE. CONCLUSION: Sarcopenia is an independent predictor of DGE after pancreaticoduodenectomy.

Inguinoscrotal hernia containing the urinary bladder successfully repaired using laparoscopic transabdominal preperitoneal repair technique: A case report.

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.

[Surgical Resection and Adjuvant Chemotherapy with FOLFOX6 for Primary Duodenal Adenocarcinoma and Nodal Metastasis Resulted in Complete Remission].

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.

Successful treatment of a patient with an infected urachal remnant via single-incision laparoscopic surgery: Report of a case.

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.

Successful treatment of conversion chemotherapy for initially unresectable synchronous colorectal liver metastasis.

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.

Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation.

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.

A case of endometriosis of the appendix.

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 plays essential roles in liver development by regulating sinusoidal endothelial cell fenestration.

UNLABELLED: 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. CONCLUSION: Cas plays pivotal roles in liver development through the reorganization of the actin cytoskeleton and formation of fenestrae in SECs.

Functional analysis of Src homology 3-encoding exon (exon 2) of p130Cas in primary fibroblasts derived from exon 2-specific knockout mice.

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.