Lymph node metastasis in T1 colorectal cancer: Risk factors and prediction model.

Endoscopic resection is typically performed for early T1 stage colorectal cancer (T1 CRC). Additional surgery is subsequently recommended based on pathological findings; however, the current criteria may result in overtreatment. The present study aimed to re-examine the reported risk factors for lymph node (LN) metastasis in T1 CRC and develop a prediction model using a large multi-institutional dataset. In this retrospective study, the medical records of 1,185 patients with T1 CRC who underwent surgery between January 2008 and December 2020 were investigated. Slides pathologically re-assessable for additional risk factors were re-examined. A total of 251 patients with inadequate data were excluded, and 934 patients were randomly assigned at a ratio of 3:1 to the training and validation datasets. In the univariate analysis, left-sided CRC (P=0.003), deep submucosal invasion depth (P=0.005), poor histological grade (P=0.020), lymphatic invasion (P<0.001), venous invasion (P<0.001) and tumor budding grade 2/3 (P<0.001) were significant risk factors for LN metastasis. A nomogram predicting LN metastasis was developed using these variables, with an area under the received operating characteristic curve (AUC) of 0.786. The nomogram was validated using a validation set with an AUC of 0.721, indicating moderate accuracy. No LN metastases were observed in patients with <90 points using the nomogram; therefore, patients with a low nomogram score may avoid undergoing surgical resection. Prediction of LN metastasis using this developed nomogram may help identify patients who are at high-risk who require surgery.

[A Case of Gastric Submucosal Tumor at Esophagogastric Junction Resected by Endoscopic Intragastric Surgery].

We report a case in which a gastric submucosal tumor at the esophagogastric junction was resected by endoscopic intragastric surgery with minimally invasive and function-preserving. A 30s-year-old man was referred to our hospital because of an abnormal findings pointed by a barium examination at a health check up. Upper gastrointestinal endoscopy and endoscopic ultrasound revealed a submucosal tumor approximately 60 mm in size on the posterior wall of the gastric fundus. Endoscopic ultrasound-fine needle aspiration was carried out and pathological result was a leiomyoma. The tumor was an intraluminal and extraluminal growth extending from the dorsal esophagus to the cardiac region, but considering the patient's young age, we decided to perform endoscopic intragastric surgery to preserve the function of stomach. A 30 mm median incision was made above the umbilicus, and the anterior wall of the gastric body was incised and the intragastric surgery was started using the double protector method. The mucosal surface of the tumor was located at the fundus, but the tumor developed into the dorsal aspect of the lower esophageal muscle layer. The tumor was carefully dissected and resected by intragastric manipulation. Postoperative oral contrast examination revealed no obvious stenosis, and gastric peristalsis was normal.

A phase II study of neoadjuvant capecitabine, oxaliplatin, and irinotecan (XELOXIRI) in patients with locally advanced rectal cancer.

Purpose: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (XELOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC. Methods: Patients received neoadjuvant irinotecan and oxaliplatin and capecitabine and then underwent total mesorectal excision. The primary study endpoint was the pathological complete response (pCR) rate. Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-two (77.8%) of 54 completed the study protocol. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%. Conclusion: XELOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS, and measures of safety met current standards.

[A Case of Giant Mesenteric Lymphangioma in an Adult].

A 26-year-old man with left inguinal pain and frequent urination was examined. An abdominal ultrasound revealed a cystic lesion. In further examinations, CT and MRI showed a large cystic lesion of about 20 cm in size, connected to mesenteric- derived blood vessels. We suspected a huge mesenteric lymphangioma and decided to perform a laparotomy. A tumor was seen in the mesentery of the jejunum and adhered to the duodenum widely. The tumor could be removed safely without resection of the duodenum by first sucking the contents and shrinking the tumor. The final pathological diagnosis was mesenteric lymphangioma. Adult mesenteric lymphangiomas measuring larger than 20 cm are relatively rare. We review the case in the context of the relevant literature.

[A Case of Gastric Anisakiasis That Required Differentiation from Scirrhous Gastric Cancer].

A 36-year-old woman visited a previous doctor with lower abdominal pain and nausea. Her former doctor's upper gastrointestinal endoscopy and CT scan showed giant folds and wall thickening of the lower body of the stomach, and she was referred on suspicion of scirrhous gastric cancer. Similar findings were found on enhanced CT at our hospital. Endoscopic findings performed several days later showed red and thickened mucosa at the cardia, but no wall thickening and giant fold, and there were no findings suggestive of scirrhous gastric cancer. Biopsy showed no atypical cells, and a large number of eosinophils appeared in the lesion at the cardia. Eosinophilia and anisakis IgE antibody were positive and a diagnosis of gastric anisakiasis was made. She was eating grilled horse mackerel the day before her stomachache. At the same time, pruritus and edema around her right knee also appeared, and a dermatologist diagnosed her with anisakis-related eosinophil edema. One month later, CT scan and endoscopy were almost normal. A young woman referred on suspicion of scirrhous gastric cancer experienced a rare case diagnosed with gastric anisakiasis.

[Radical Resection Was Achieved Using a Liver-First Approach for Simultaneous Liver Metastasis from Rectal Cancer-A Case Report].

The patient was a 70s male. A fecal occult blood test showed a positive reaction, and colonoscopy was performed. Under a diagnosis of rectal cancer, he was referred to our hospital. Detailed examination revealed solitary liver metastasis measuring 60 mm and involving the S4 to S1 areas of the liver. A strategy to perform systemic chemotherapy in advance was adopted. Five courses of FOLFOXIRI therapy were conducted, and a partial response(PR)was achieved, suggesting that the tumor is resectable. Extended left/caudal lobectomy was performed. There was no complication, and the patient was discharged. After 4 months, laparoscopic low anterior resection and temporary ileostomy were conducted. According to the TNM staging, the grade was evaluated as ypT2N0. On histological response evaluation, the grade was evaluated as 1a. The stoma was closed. During the 1.5-year follow-up after initial treatment, there has been no relapse. We encountered a patient with simultaneous liver metastasis from rectal cancer in whom the use of a liver-first approach(LFA)after systemic chemotherapy facilitated radical resection. The present case suggested that the LFA contributes to a rise in the resection rate, further improving the prognosis.

[Laparoscopic Abdominoperineal Resection with the Trans-Perineal Approach for Anal Canal Cancer in a Patient with Situs Inversus Totalis-A Case Report].

Situs inversus totalis(SIT)is a rare congenital condition that causes complete transposition of thoracic and abdominal viscera. Due to associated anatomical abnormalities and low frequency, surgery for affected patients is considered to be difficult. A 72-year-old man was referred to our hospital with a chief complaint of narrow stools. The diagnosis was anal canal cancer(cT1bN0M0)accompanied by SIT. A trans-perineal minimally invasive surgical procedure with laparoscopic abdominoperineal resection(Tp-APR)was performed. When mobilizing the sigmoid colon, the surgeon changed their position in consideration of anatomical abnormalities. On the other hand, manipulation around the rectum was possible using the same technique as in patients with normal anatomy. The postoperative course was uneventful, and he had no recurrence 18 months after surgery. This is the first case that showed Tp-APR for anal canal cancer with SIT performed safely and feasibly. Preoperative simulation of associated abnormal anatomical structures is considered crucial for a case of SIT.

Randomized phase II study of SOX+B-mab versus SOX+C-mab in patients with previously untreated recurrent advanced colorectal cancer with wild-type KRAS (MCSGO-1107 study).

BACKGROUND: Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS. METHODS: This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled. RESULTS: Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively). CONCLUSIONS: The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen. TRIAL REGISTRATION: UMIN Clinical Trials Registry ( UMIN000006706 ). Date of registration: NOV/11/2011. URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920.

[A Case of Advanced Gastric Cancer with Distant Lymph Nodes Metastasis Showing a Complete Response to Six-Courses Chemotherapy].

This study reports a 66-year-old female presenting abdominal pain. Gastrointestinal endoscopy showed the presence of a type 3 tumor in the lesser curvature of the stomach, and biopsy revealed poorly differentiated adenocarcinoma. CT images displayed thickening of the stomach wall and enlarged paraaortic lymph nodes, left supraclavicular lymph nodes, and left iliac lymph nodes. FDG-PET/CT scan showed abnormal accumulation at the same site. The patient was diagnosed with unresectable highly advanced gastric cancer(cT4aN2H0P0M1[LYM], Stage Ⅳ). She was treated with combination chemotherapy of S-1 and CDDP(SP). Tumor markers normalized(CA19-9 11,158→20 U/mL)after 3 courses with a marked reduction of lesions. After 5 courses of chemotherapy, the tissue biopsy did not reveal any cancer and a complete response(CR) was achieved. Adverse events of diarrhea and loss of appetite were observed. Subsequently, chemotherapy was discontinued after 6 courses, and CR remained for the next 5 years. Thus, we experienced a rare case of unresectable advanced gastric cancer with distant lymph nodes metastasis, showing long-term recurrence-free survival after receiving 6 courses of SP chemotherapy.

[A Case of Internal Hernia Incarceration of a Mesenteric Defect following Laparoscopic Ileocecal Resection].

A 75-year-old man underwent laparoscopic ileocecal and partial small bowel resections for the management of appendiceal cancer. The pathological diagnosis was cecal cancer(T4b[ileum, abdominal wall],N0[0/13], M0, pStage Ⅱc). After 4 months of surgery, he suddenly experienced abdominal pain and vomiting and was presented to our emergency room. He was diagnosed with bowel obstruction following which, conservative treatment was initiated through a nasogastric ileus tube implantation; however, he did not show any improvement. Subsequently, he underwent experimental laparotomy on the 18th day of the disease. Intraabdominal examination revealed herniated small intestine through a mesenteric defect, which was closed following repositioning of the herniated small intestine. The postoperative course was good, and the patient was discharged on the 10th day after surgery. No recurrence of intestinal obstruction has been observed after 1 year and 6 months. Closure of the mesenteric defect, although not commonly performed in laparoscopic colorectal surgery, is worth considering because of the risk of developing an internal hernia requiring surgical treatment, as in our case.

[Surgical Technique for Prevention of Incisional Hernia in Laparoscopic Small Bowel Resection in the Obese Patient].

A 67-year-old woman reporting lower abdominal pain and anemia was examined. Small intestinal tumor was diagnosed by small intestinal radiographic contrast study and small intestinal endoscopy, and we decided to perform a laparoscopic partial resection of the small bowel. Since she was obese patients(BMI 36.3, abdominal wall 6 cm)at high risk of postoperative incisional hernia, we devised a way to make the wound smaller. We judged thick abdominal wall make umbilical wound larger in single port surgery. We performed multi-port surgery by using one 15 mm trocar, and removed small intestinal tumor from 15 mm port incision. In addition, to prevent incisional hernia, we used a trocar with a wound closure assist function for securely closing the port wound in all layers. Histopathological diagnosis was neuroendocrine tumor. The patient is being followed up without recurrence and without incisional hernia. In partial small bowel resection of obese patient, the use of a 15 mm port to minimize wound site and the use of trocar with a wound closure assist function may lead to prevent incisional hernia.

Evaluation of FOLFOX or CAPOX reintroduction with or without bevacizumab in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy (REACT study).

BACKGROUND: Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. METHODS: Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3-79.3) and the DCR was 82.8% (95% confidence interval 64.2-94.2). The RR for oxaliplatin-free interval was 100.0% in months 6-12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. CONCLUSION: Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.

[Laparoscopic Tumor Resection for Retroperitoneal Leiomyosarcoma-A Case Report].

A 59-year-old man visited our department because of cholecystectomy. Preoperative CT revealed a tumor shadow measuring 50 mm in front of the right iliopsoas muscle. MRI showed a low signal intensity on T1-weighted images and a slightly high signal intensity on the T2-weighted image. PET-CT showed accumulation of FDG(SUVmax 5.39)in the tumor but no other abnormal accumulations. We performed tumor resection for diagnostic purposes because malignancy could not be ruled out owing to the large size of the mass. Intraoperative findings showed a well-circumscribed margin of the tumor without invasion to other tissues. The retroperitoneum was incised circumferentially along the tumor under laparoscopic guidance, and the tumor was resected. Histopathological and immunostaining findings were consistent with leiomyosarcoma. In laparoscopic surgery, the surgical margin is observed in detail through the magnifying effect. Therefore, laparoscopic surgery can be a surgical option for tumors that may be completely excised based on preoperative findings.

[A Case of Fibrolamellar Hepatocellular Carcinoma in a 25-Year-Old Vietnamese Male].

We report a rare case of hepatic fibrolamellar hepatocellular carcinoma(FLC). A 25-year-old Vietnamese male experienced loss of appetite and abdominal pain. He was referred for further examination of a 20 cm tumor in the left lobe of the liver detected in mass screening ultrasonography. He tested negative for HBs-antigen and HCV-antibody. The serum PIVKA- Ⅱ level was elevated. Liver function test findings were normal. The arterial phase of contrast enhanced abdominal CT revealed a 20×30 cm tumor that was well-enhanced, except for a central scar in the left lobe of liver. Enhanced MRI showed a high intensity tumor. T2-weighted MRI showed an iso-intensity tumor with a low-intensity central fibrous scar. Upon diagnosing the patient with FLC, we performed left hepatic trisegmentectomy. Pathological findings of the surgical specimen showed eosinophilic large neoplastic cells surrounded by fibrous stroma arranged in a lamellar fashion. This confirmed the diagnosis. FLC, which occurs in noncirrhotic livers of young patients, is a distinct clinicopathological variant of hepatocellular carcinoma. Hepatectomy for FLC should be accompanied with regional lymphadenectomy because of its association with lymph node metastasis. We also reviewed cases reported in Japan.

[Laparoscopic Surgery for Synchronous Retroperitoneal Tumor and Ovarian Mature Teratoma-A Case Report].

A 72-year-old woman was transferred to our hospital after being diagnosed with retroperitoneal and ovarian tumors. Abdominal computed tomography revealed a well-defined mass lesion measuring 35 mm on the dorsal side of the descending part of the duodenum that was surrounded by the head of the pancreas and inferior vena cava. In addition, a cystic mass measuring 90 mm was found in the pelvis. Hence, the patient was diagnosed synchronous retroperitoneal tumor and teratoma. Laparoscopic retroperitoneal tumor resection and right adnexectomy were performed. The pathological findings indicated that the retroperitoneal tumor was a diffuse large B-cell lymphoma and the pelvic tumor was a mature cystic teratoma of the ovary. On the basis of the computed tomography findings, we judged that the tumor had a poor tendency to infiltrate and could be peeled off and resected using laparoscopic surgery. In this rare case, the retroperitoneal tumor and mature teratocarcinoma were simultaneously resected laparoscopically.

Development of a novel prediction model for recurrent stage II colon cancer.

PURPOSE: Adjuvant chemotherapy is recommended for patients with high-risk stage II colon cancer. High-risk stage II is defined by clinicopathological factors in some guidelines. However, there is no unified definition. The aim of this study was to examine the risk factors and develop a novel model to predict the recurrence of stage II colon cancer. METHODS: Three hundred fifty patients who underwent curative resection for stage II colon cancer at Osaka International Cancer Institute and Yao Municipal Hospital from 2004 to 2012 were included. Clinicopathological factors were assessed in a subgroup of 298 patients (Learning Set), and the relapse-free survival (RFS) rate was evaluated as the main outcome. A statistical analysis was performed using a proportional hazards model to determine the factors associated with RFS and a nomogram was developed to predict recurrence. A second subgroup of 52 independent patients who underwent curative resection in 2012 (Validation Set) was used to validate the nomogram. RESULTS: The median RFS time was 4.96 years, and recurrence was observed in 35 patients. A univariate analysis revealed that a high serum CEA level, preoperative occlusion, tumor location (left-side colon), lymphatic invasion, and vascular invasion were significantly correlated with RFS. These variables were used to develop the nomogram. The C-index was 0.701 in the learning set and 0.585 in the validation set. Using nomogram points, the patients were classified into low-risk, middle-risk, and high-risk categories. CONCLUSION: A recurrence prediction model was developed that integrated multiple risk factors in stage II colon cancer patients. High-risk patients were identified by the nomogram.

Efficacy and safety of anticoagulant prophylaxis for prevention of postoperative venous thromboembolism in Japanese patients undergoing laparoscopic colorectal cancer surgery.

AIM: To investigate the efficacy and safety of anticoagulant prophylaxis to prevent postoperative venous thromboembolism (VTE) during laparoscopic colorectal cancer (CRC) surgery, which is unknown in Japanese patients. METHODS: We conducted this randomized controlled trial at nine institutions in Japan from 2011 to 2015. It included 302 eligible patients aged 20 years or older who underwent elective laparoscopic surgery for CRC. Patients were randomly assigned to an intermittent pneumatic compression (IPC) therapy group or to an IPC + anticoagulation therapy group. Anticoagulation therapy comprised fondaparinux or enoxaparin for postoperative VTE prophylaxis. Postoperative VTE was diagnosed based on enhanced multi-detector helical computed tomography. The primary endpoint was VTE incidence, including asymptomatic cases, the secondary endpoint was incidence of major bleeding, and we conducted an intention-to-treat analysis. This study is registered in UMINCTR (UMIN000008435). RESULTS: Postoperative VTE incidence was 5.10% with IPC therapy (n = 157) and 2.76% with IPC + anticoagulant therapy (n = 145; P = .293). We identified no symptomatic VTE cases. The major bleeding rates were 1.27% with IPC alone and 1.38% with the combination (P = .936). The overall bleeding rates were 7.69% for enoxaparin and 13.6% for fondaparinux (P = .500), and there were no bleeding-related deaths. CONCLUSION: Anticoagulant prophylaxis did not reduce the incidence of VTE and the incidence of major bleeding was comparable between the two groups. Usefulness of perioperative anticoagulation was not demonstrated in this study. Pharmacological prophylaxis must be restricted in Japanese patients with higher risk of VTE.

Erratum: A novel prognostic prediction model for recurrence in patients with stage II colon cancer after curative resection.

[This corrects the article DOI: 10.3892/mco.2018.1733.].

[A Case of Recurrence in the Lateral Pelvic Lymph Node after Local Excision of Lower Rectal pT1a Cancer].

The patient was a man in his 70s who visited our hospital to undergo an examination for fecal occult blood, which detected a 20 mm, Ⅱa lesion in the lower rectum on colonoscopy. He was diagnosed with SM-invasive cancer and was planned to undergo trans-anal local excision. After the surgery, he had a good postoperative course without complications. The pathological findings were Ⅱa, tub1, 22×16 mm, pT1a(950 mm), int, INF a, ly0, v0, pHM0, pVM0(300 mm). He was followed up after the surgery, but was diagnosed with lateral lymph node recurrence 4 years after a local surgery. The surgery involved right-sided lateral lymphadenectomy with resection of the ureter, spermatic duct, seminal vesicle, and piriformis muscle. He was diagnosed with lymph node metastasis with invasion of the spermatic duct based on pathology. Eight courses of adjuvant chemotherapy containing CapeOX was administered. Unfortunately, primary squamous cell lung cancer was detected, and he died after surgery for recurrence in the second year. It is suggested that it is necessary to note lateral lymph node recurrence on postoperative follow-up for lower rectal cancer at any stage.