[Results of Watch and Wait after Chemoradiotherapy for Locally Advanced Rectal Cancer].

BACKGROUND: Watch and wait(W & W)for rectal cancer after chemoradiotherapy(CRT)is attracting attention. PURPOSE: To examine regimens and indications from the results of follow-up of cases undergoing W & W in our department. MATERIALS AND METHODS: CRT(SOX therapy 2-5 cycles, 45 Gy)was performed on patients with lower rectal cancer over a period of 2016 to 2020, and 7 patients with clinical complete response(cCR)were followed up. RESULTS: With a median follow-up of 33 months(10-74), 4 of 7 patients(57.1%)remained in cCR. Two patients had local relapse more than a year after the start of treatment, were able to undergo salvage surgery, and are alive after surgery. Patients with lateral lymph node metastasis before CRT had para-aortic lymph node metastasis at 8 months. CONCLUSIONS: Patients with maintained cCR were those with localized, node-negative disease. On the other hand, in patients with lymph node metastasis, including lateral metastasis, it was not possible to perform salvage surgery due to distant metastasis. Careful case selection and follow-up are necessary in the future.

[A Case of the Huge GIST in the Transverse Colon Mesentery with Intra-Tumoral Hemorrhage and Jejunal Infiltration].

A 38-year-old woman was admitted to our hospital due to severe anemia. CT showed a 13×12 cm tumor with moderately enhanced wall thickening in the right upper abdomen. The huge tumor located adjacent to the jejunum and compressed the right transverse colon. Hemorrhagic necrosis and air were observed within the tumor, suspecting tumor penetration into the jejunum. The patient was diagnosed with abdominal GIST with jejunal infiltration. Laparotomy revealed a 13× 11 cm solid mass with intra-tumoral hemorrhage and invasion into the jejunum, located in the transverse mesocolon. Tumor resection combined with partial jejunectomy and transverse colectomy were performed. Immunohistochemical findings of the resected specimen was positive for c-kit and DOG-1, and the MIB-1 positive rate was 10%. Three weeks after the operation, re-anastomosis was performed due to transverse colon anastomotic stricture. She was discharged 45 days after first operation. Currently, 9 months after the operation, patient has been prescribed imatinib and is alive without recurrence.

Hyperdry Human Amniotic Membrane as a Protective Dressing for Open Wounds With Exposed Bowel in Mice.

INTRODUCTION: An enteroatmospheric fistula forms when the exposed bowel is perforated with chronic enteric fistula formation. Currently, there is no established preventative method for this condition. Hyperdry (HD) amniotic membrane (AM) can promote early granulation tissue formation on the exposed viscera and is suitable for dressing intractable wounds as it possesses anti-inflammatory, antibacterial, and immunomodulatory properties. This study investigated whether HD-AM promotes early formation of blood vessel-containing granulation tissue for enteroatmospheric fistula treatment. METHODS: An experimental animal model of an open wound with exposed bowel was developed. A 15 × 20 mm wound was prepared on the abdomen of Institute of Cancer Research mice, and the HD-AM was placed. The mice were assigned to one of the following groups: HD-AM group, in which the stromal layer of the HD-AM was placed in contact with the exposed bowel; HD-AM UD group, in which the epithelial layer of the HD-AM was placed in contact with the exposed bowel; and the HD-AM (-) or control group, in which the HD-AM was not used. RESULTS: On postoperative days 7 and 14, granulation tissue thickness significantly increased in the HD-AM and HD-AM UD groups compared with that in the HD-AM (-) group. Macrophages accumulated in the HD-AM epithelium only in the HD-AM group. During HD-AM contact, a subset of invading macrophages switched from M1 to M2 phenotype. CONCLUSIONS: HD-AM is a practical wound dressing with its scaffolding function, regulation of TGF ß-1 and C-X-C motif chemokine 5 (CXCL-5), and ability to induce M1-to-M2 macrophage conversion.

[A Case of Pancreatic Tail Cancer Causing Gastrointestinal Hemorrhage Due to Transverse Colon Invasion].

An 81-year-old woman was admitted to our hospital due to frequent bleeding and hemorrhagic shock. Blood tests revealed anemia and contrast-enhanced abdominal CT revealed a pancreatic tail tumor with a diameter of 60 mm. The boundary between pancreatic tumor and the transverse colon, stomach and spleen was unclear, and invasion of the transverse colon as well as the stomach and spleen was suspected. Hemorrhage due to colon invasion of the pancreatic tail cancer and intra-tumoral hemorrhage were suspected. Due to persistent bleeding, the patient had emergency surgery to control bleeding. The pancreatic tail tumor invaded not only the colon but also stomach and spleen, distal pancreatectomy, partial gastrectomy and splenectomy was performed in combination with resection of the transverse colon, and transverse colon colostomy. We report a case of gastrointestinal bleeding caused by transverse colon invasion of pancreatic tail cancer, which resulted in emergency surgery.

[A Case of Perihilar Cholangiocarcinoma with Postoperative Hepatic Encephalopathy Due to Portosystemic Shunt Treated by Percutaneous Embolization].

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.

Timing of indocyanine green injection prior to laparoscopic colorectal surgery for tumor localization: a prospective case series.

BACKGROUND: Accurate identification of tumor sites during laparoscopic colorectal surgery helps to optimize oncological clearance. We aimed to assess the timing of the local injection preoperatively and clarify the usefulness and limitation of tumor site marking using indocyanine green (ICG) fluorescence imaging. METHODS: Consecutive patients who underwent primary colorectal cancer surgery from September 2017 to January 2019 were included. Preoperatively, lower endoscopy was used to inject the ICG solution into the submucosal layer near the tumor. During laparoscopic surgery, ICG fluorescence marking as the tumor site marking was detected using a laparoscopic near-infrared camera system. The detection rate and factors associated with successful intraoperative ICG fluorescence visualization including the interval between local injection and surgery were evaluated. RESULTS: One hundred sixty-five patients were enrolled. Using the laparoscopic near-infrared system, the intraoperative detection rates of ICG marking were 100% for ICG injection within 6 days preoperatively, 60% for injection between 7 and 9 days preoperatively, and 0% for injection earlier than 10 days preoperatively. There were no complications associated with ICG marking. Additionally, this method did not disturb the progress of the surgical procedure because injected ICG in the submucosal layer did not cause any tissue inflammation, and if ICG spilled into the serosa, it was invisible by white light. CONCLUSION: Advantages of ICG fluorescence tumor site marking were high visibility of infrared imaging during laparoscopic colorectal surgery and minimal adverse events of surgery. One of the most important findings regarding practical use was a rapid decrease in fluorescence marking visibility if one week passed from the time of ICG local injection.

Efficacy of indocyanine green fluorescence angiography in preventing anastomotic leakage after laparoscopic colorectal cancer surgery.

PURPOSE: Some recent studies have suggested that fluorescence angiography with indocyanine green (ICG) might be useful for preventing anastomotic leakage (AL) after laparoscopic colorectal surgery. However, its efficacy has not been proven. We evaluated whether intraoperative ICG fluorescence angiography could decrease the AL rate with laparoscopic colorectal cancer surgery. METHODS: This retrospective study included patients with colorectal cancer who underwent laparoscopic surgery at our institution between March 2014 and December 2018. Patients were divided into two groups: with or without ICG fluorescence angiography. The primary outcome was the rate of AL. RESULTS: A total of 488 patients were included: 223 patients in the ICG group and 265 patients in the no-ICG group. In the ICG group, the transection line was changed to a more proximal location in seven patients (3.1%), including one patient with transverse colon surgery and six with rectal surgery. None of these seven patients developed AL. There were 18 ALs (3.7%) overall. The AL rate was 1.8% in the ICG group and 5.3% in the no-ICG group. For colon cancer, there were no significant differences in the AL rate between the groups (p = 0.278). In rectal cancer, the AL rate was significantly lower in the ICG group than in the no-ICG group (3.5% vs. 10.5%, p = 0.041). After propensity score matching, the AL rate was also significantly lower in the ICG group for rectal cancer (p = 0.044). CONCLUSION: ICG fluorescence angiography can potentially reduce the AL rate with laparoscopic rectal cancer surgery.

Transforming Growth Factors α and ß Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model.

To gain insight into the cellular and molecular interactions mediating the desmoplastic reaction and aggressive malignancy of mass-forming intrahepatic cholangiocarcinoma (ICC), we modeled ICC desmoplasia and progression in vitro. A unique three-dimensional (3D) organotypic culture model was established; within a dilute collagen-type I hydrogel, a novel clonal strain of rat cancer-associated myofibroblasts (TDFSM) was co-cultured with a pure rat cholangiocarcinoma cell strain (TDECC) derived from the same ICC type as TDFSM. This 3D organotypic culture model reproduced key features of desmoplastic reaction that closely mimicked those of the in situ tumor, as well as promoted cholangiocarcinoma cell growth and progression. Our results supported a resident liver mesenchymal cell origin of the TDFSM cells, which were not neoplastically transformed. Notably, 3D co-culturing of TDECC cells with TDFSM cells provoked the formation of a dense fibrocollagenous stroma in vitro that was associated with significant increases in both proliferative TDFSM myofibroblastic cells and TDECC cholangiocarcinoma cells accumulating within the gel matrix. This dramatic desmoplastic ICC-like phenotype, which was not observed in the TDECC or TDFSM controls, was highly dependent on transforming growth factor (TGF)-ß, but not promoted by TGF-α. However, TGF-α was determined to be a key factor for promoting cholangiocarcinoma cell anaplasia, hyperproliferation, and higher malignant grading in this 3D culture model of desmoplastic ICC.

Validation of the Japanese Version of the Low Anterior Resection Syndrome Score.

BACKGROUND: The low anterior resection syndrome (LARS) score is a patient-reported outcome measure to evaluate the severity of bowel dysfunction after rectal cancer surgery by scoring the major symptoms of LARS. The aim of this study was to translate the English version of the LARS score into Japanese and to investigate the validity and reliability of the LARS score. METHODS: The LARS score was translated in Japanese following current international recommendations. A total of 149 rectal cancer patients completed the LARS score questionnaire and were also asked a single question assessing the impact of bowel function on quality of life (QoL). A total of 136 patients answered the LARS score questionnaire twice. RESULTS: The Japanese LARS score showed high convergent validity, based on its good correlation between the LARS score and QoL (p < 0.001). The LARS score was able to discriminate between patients according to the tumor distance to anal verge (p < 0.001), type of surgery (p < 0.001), and time since surgery (p = 0.001). Patients after ultra-low anterior resection and intersphincteric resection showed especially high scores. The score also had high test-retest reliability (intraclass correlation coefficient: 0.87). CONCLUSION: The Japanese LARS score is a valid and reliable tool for measuring LARS. The LARS score is appropriate for assessments in postoperative bowel function and international comparison. Using this score, patient-reported outcome measures of LARS in Japanese patients can be shared internationally. Additional validation reports from non-English speaking countries can support the LARS score as a worldwide assessment tool for postoperative bowel dysfunction.

Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma.

BACKGROUND: The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC). METHODS: We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed. RESULTS: The Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor. CONCLUSION: HMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.

[A Case of Laparoscopic Resection of Sigmoid Colon Cancer Complicated by an Iliopsoas Abscess Preceded by Abscess Drainage].

For colon cancer complicated by iliopsoas abscess, it is unclear whether surgery should be performed prior to abscess drainage. We were able to perform laparoscopic sigmoid resection safely after first draining the abscess. We believed it would be beneficial to avoid surgery in the presence of abscess and inflammation, and the minimally invasive operation was performed after improvements of the patient's general status and inflammation.

[Damage Control Surgery for Perforation of Colon Cancer].

Perforation due to colon cancer maycause peritonitis and septic shock. In these cases, we maynot be able to rescue the patients in spite of emergencysurgical intervention; in these conditions, owing to limitations of operation time, it is difficult for us to assess the state or extent of the disease and to perform an ideal oncological surgerywith dissection of lymph nodes. To overcome these limitations, we introduce the concept of "damage control surgery" developed in the trauma region to treat perforations of colon cancer. There are 3 steps: first, the perforated intestine is resected and the peritoneal cavityis lavaged to control contamination. Open abdominal management is used as a temporaryabdominal closure; second, sepsis is treated in the ICU; and third, based on the treatment strategydecided upon after consulting a colorectal surgeon and the patient's family, a colostomy, anastomosis, and extra dissection of lymph node are performed before abdominal closure. We report the fatal case of a 92-year-old woman who had developed severe shock to indicate the significance of this strategy.

[A Case of Disseminated Carcinomatosis of the Bone Marrow with Disseminated Intravascular Coagulation Caused by Cecal Cancer Successfully Treated with mFOLFOX6].

Disseminated carcinomatosis of the bone marrow is often accompanied by disseminated intravascular coagulation syndrome (DIC). This condition is rarely caused by colorectal cancer, and there are no established therapies. OUR CASE: A 66-year-old woman was admitted to our hospital because of DIC. She had been diagnosed with cecal cancer and multiple metastases of the lymph nodes, liver, and bone. She was diagnosed with disseminated carcinomatosis of the bone marrow and treated with systemic chemotherapy by modified FOLFOX6 (mFOLFOX6). Subsequently, the DIC rapidly resolved, and she was discharged from the hospital.

Total Synthesis of Mycalolides A and B through Olefin Metathesis.

An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides A and B is described. This synthesis involves the convergent assembly of highly functionalized C1-C19 trisoxazole and C20-C35 side-chain segments through the use of olefin metathesis and esterification as well as Julia-Kocienski olefination and enamide formation as key steps.

Chondroma of the diaphragm mimicking a giant liver tumor with calcification: report of a case.

Extraskeletal chondroma is an unusual benign tumor, which rarely arises in the diaphragm. We report a case of chondroma of the diaphragm in a 31-year-old woman. Initially, a benign liver tumor with calcification was suspected, based on pre and intraoperative examination findings. Although parts of the tumor were contiguous with the diaphragm, its connections with the diaphragm were much narrower than its connection with the liver, which suggested a liver tumor. Pathological examination subsequently revealed that the chondroma was contiguous with the diaphragm and that there was a distinct border between the tumor and the liver; thus, the tumor was diagnosed as a chondroma of the diaphragm.

[A case of metastatic colorectal cancer that reduced in size after re-challenging with an anti-EGFR monoclonal antibody].

A 58-year-old woman was confirmed as having multiple liver metastases after undergoing a high anterior resection for a sigmoid colon tumor. She was administered bevacizumab+FOLFOX as the first regimen and bevacizumab+FOLFIRI and S-1 and irinotecan (IRIS)therapy as the second regimen. During this treatment she also underwent hepatectomy 3 times and radiofrequency ablation once. She was administered panitumumab+irinotecan as the third regimen and, due to the presence of multiple pulmonary metastases, was subsequently considered to have had a partial response (PR). Because she subsequently developed progressive disease (PD), she received the fourth regimen as part of a clinical trial (TAS102) in another hospital. Cetuximab+irinotecan was administered as the fifth regimen after PD and the tumor was found to have reduced in size by 23%upon computed tomography (CT) 2 months later. Although stable disease (SD) was achieved, she was subsequently administered regorafenib for 8 months as a sixth regimen after the disease progressed a second time. In some cases of KRAS wild type metastatic colorectal cancer, re-challenging with an anti-epidermal growth factor receptor (EGFR) monoclonal antibody seems to be an effective strategy for reducing tumor mass.

Splenic rupture after surgical fixation of rib fractures with video-assisted thoracoscopic surgery: A case report.

INTRODUCTION: Recently, the utilization of surgical stabilization of rib fractures (SSRF) with video-assisted thoracoscopic surgery (VATS) has been increasing owing to its effectiveness. The present report describes the case of a patient who underwent SSRF with VATS and subsequently developed a splenic rupture that was speculated to be related to intrathoracic manipulation during surgery. PRESENTATION OF CASE: A 62-year-old male patient sustained injuries from a fallen festival car over his thoracoabdominal zone and was diagnosed with bilateral multiple rib fractures and burst fractures of the twelfth thoracic and first lumbar vertebrae. The patient underwent SSRF with VATS. Following surgery, the patient went into hemorrhagic shock due to a splenic rupture, necessitating an emergency open splenectomy. DISCUSSION: Despite no initial detection of splenic injury on contrast-enhanced CT, it is possible that a slight splenic injury existed at the time of the initial diagnosis. Moreover, during surgery, additional external forces may have been applied to the spleen due to positional changes, such as shifting to the lateral position or retracting the diaphragm using forceps; these manipulations could have potentially caused a slight splenic injury, possibly leading to splenic rupture. CONCLUSION: When performing SSRF through VATS, it is important to recognize that manipulation and traction of the diaphragm could potentially cause splenic rupture, even if a slight force is applied. Therefore, the diaphragm should be evaluated without traction and manipulation whenever possible.

An ampullary adenoma presenting with jaundice caused by duodenal intussusception: a case report.

BACKGROUND: Ampullary adenomas are premalignant lesions. However, biliary obstruction causing jaundice is rare. Duodenal intussusception secondary to an ampullary adenoma rarely occurs because of the fixed position of the duodenum in the retroperitoneum. Herein, we have described a rare case of ampullary adenoma with jaundice caused by duodenal intussusception. CASE PRESENTATION: A 40-year-old woman presenting with vomiting and yellowish discoloration of the skin was admitted to another hospital. The patient had experienced recurrent epigastric pain and vomiting for the past 18 months. Blood test results showed elevated levels of bilirubin (3.9 mg/dL), and abdominal computed tomography (CT) showed a 60-mm hypovascular mass in the third part of the duodenum and a left lateral shift of the dilated common bile duct. The patient was referred to our hospital for further evaluation. She recovered from hyperbilirubinemia spontaneously (levels of bilirubin, 1.0 mg/dL), and the CT showed a tumor shift from the third part of the duodenum to the second part and improvement of the dilated common bile duct. Hypotonic duodenography revealed a tumor that moved easily from the second to the third portion of the patient's position. Upper gastrointestinal endoscopy revealed a large papillary tumor occupying the second part of the duodenum, which was diagnosed as an adenoma through biopsy. The possibility of malignancy could not be negated owing to the presence of jaundice and an elevated carbohydrate antigen 19-9 level (76.0 U/mL). Pancreaticoduodenectomy was performed. The resected specimen showed a 60 × 40 × 40-mm pedunculated ampullary mass with submucosal elongation. The pathological examination indicated that the ampullary tumor was a high-grade intestinal adenoma. The postoperative course was uneventful, and the patient was discharged 26 days postoperatively. CONCLUSIONS: This report describes a rare case of a patient with an ampullary adenoma presenting with jaundice resulting from duodenal intussusception. Owing to the possibility of a postoperative cancer diagnosis which may have caused the biliary obstruction and the difficulty in making an accurate preoperative diagnosis, it is imperative to choose the appropriate surgical procedure such as a pancreaticoduodenectomy.

A Randomized Trial of Ionic Silver Dressing to Reduce Surgical Site Infection After Gastrointestinal Surgery.

Objective: To determine whether Aquacel Ag Hydrofiber dressings containing ionic silver are superior to film dressings for preventing superficial surgical site infections (SSI) in patients undergoing elective gastrointestinal surgery. Background: Multiple clinical trials have assessed the effectiveness of silver-containing wound dressings; however, systematic reviews failed to find any advantages of these dressings and concluded that there was insufficient evidence to indicate that they prevented wound infections. This study aimed to evaluate the efficacy of Aquacel Ag Hydrofiber dressings for preventing superficial SSIs in patients undergoing gastrointestinal surgery. Methods: Patients undergoing elective gastrointestinal surgery were randomly assigned to receive either Aquacel Ag Hydrofiber (study group) or film dressings (control group). The primary end point was superficial SSI within 30 days after surgery (UMIN Clinical Trials Registry ID: 000043081). Results: A total of 865 patients (427 study group, 438 control group) were qualified for primary end-point analysis. The overall rate of superficial SSIs was significantly lower in the study group than in the control group (6.8% vs 11.4%, P = 0.019). There was no significant difference in superficial SSI rates between the groups in patients undergoing upper gastrointestinal surgery; however, the rate was significantly lower in the study group in patients undergoing lower gastrointestinal surgery (P = 0.042). Multivariate analysis identified Aquacel Ag Hydrofiber dressings as an independent factor for reducing superficial SSIs (odds ratio, 0.602; 95% confidence interval, 0.367-0.986; P = 0.044). Conclusions: Aquacel Ag Hydrofiber dressings can reduce superficial SSIs compared to film dressings in patients undergoing elective gastrointestinal surgery, especially lower gastrointestinal surgery.

Diffusely infiltrative squamous cell carcinoma of the esophagus presenting as a case with diagnostic difficulty.

We report a rare case of diffusely infiltrative squamous cell carcinoma of the esophagus. The patient, a 68-year-old man, was admitted to our hospital for investigation of dysphagia. Esophagography and upper gastrointestinal endoscopy revealed esophageal stenosis and gastric cancer. As a biopsy from the esophagus revealed no sign of malignancy, he underwent only distal gastrectomy. After 3 months, the stenosis became worse. Again, biopsy from a gastrointestinal endoscopy showed no malignancy, but endobronchial ultrasound-guided transbronchial needle aspiration revealed squamous cell carcinoma of the esophagus. Despite various treatments, the patient died of disease progression 20 months after its onset. Autopsy revealed diffusely infiltrative squamous cell carcinoma of the esophagus, which is a rare malignancy with few case reports documented.