Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study.

Aim: We report the short/mid-term results of surgery for high-risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S-1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0-2. Methods: High-risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high-resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0-3MRF-LLN- (34.3%). Curative-intent surgery was performed on 31, with sphincter-preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0-2 rates were 12.9% and 45.1%. Three-year disease-free survival rates (3yDFS) for ypT0-2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3-year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0-3MRF-LLN- and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion: NAC yielded a clinically significant effect in about half of high-risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

Microanatomical organization of hepatic venous lymphatic system in humans.

Lymphatic fluid drains from the liver via the periportal lymphatic, hepatic venous lymphatic, and superficial lymphatic systems. We performed a postmortem study to clarify the three-dimensional structure and flow dynamics of the human hepatic venous lymphatic system, as it still remains unclear. Livers were excised whole from three human cadavers, injected with India ink, and sliced into 1-cm sections from which veins were harvested. The distribution of lymphatic vessels was observed in 5 µm sections immunostained for lymphatic and vascular markers (podoplanin and CD31, respectively) using light microscopy. Continuity and density of lymphatic vessel distribution were assessed in en-face whole-mount preparations of veins using stereomicroscopy. The structure of the external hepatic vein wall was assessed with scanning electron microscopy (SEM). The lymphatic dynamics study suggested that lymphatic fluid flows through an extravascular pathway around the central and sublobular veins. A lymphatic vessel network originates in the wall of sublobular veins, with a diameter greater than 110 µm, and the peripheral portions of hepatic veins and continues to the inferior vena cava. The density distribution of lymphatic vessels is smallest in the peripheral portion of the hepatic vein (0.03%) and increases to the proximal portion (0.22%, p = 0.012) and the main trunk (1.01%, p < 0.001), correlating positively with increasing hepatic vein diameter (Rs = 0.67, p < 0.001). We revealed the three-dimensional structure of the human hepatic venous lymphatic system. The results could improve the understanding of lymphatic physiology and liver pathology.

[Short Term and Long Term Outcomes of Robotic Surgery in Sphincter Function Preserving Surgery for Lower Rectal Cancer].

BACKGROUND: Surgical and oncological outcomes of lower rectal cancer remain unsatisfactory. We investigated the short term and long term outcomes of robotic surgery for sphincter function-preserving surgery(SPS)for lower rectal cancer. METHOD: 433 lower rectal cancer patients who underwent SPS at our institution from January 2000 to July 2021 were included, excluding Stage Ⅳ cases and patients with multiple cancers. There were 288 cases of laparotomy, 81 cases of laparoscopic surgery, and 64 cases of robotic surgery; we abbreviated the group names as: OP, LAP, and R, respectively. We retrospectively reviewed the anastomotic leakage rate and prognosis of these groups. RESULTS: The anastomotic leakage rate was 23.6% in the OP group, 17.3% in the LAP group, and 6.3% in the R group, with a significant difference between the OP group and the R group. The 3-year recurrence free survival rate was 86.7% in the LAP group and 95.6% in the R group. Although there was no significant difference, the prognosis tended to be better in the R group. Local recurrence was observed in 3 patients in the LAP group and 1 patient in the R group. CONCLUSION: In SPS for advanced lower rectal cancer, robotic surgery may contribute to a reduction in anastomotic leakage.

[A Case of Robot-Assisted Laparoscopic Surgery for Stenotic Sigmoid Colon Cancer with Simultaneous Lateral Lymph Node Metastasis].

The patient is a 63-year-old man. He visited his previous physician for abdominal pain. After close examinations, he was diagnosed with stenotic sigmoid colon cancer with left lateral lymph node metastasis. On the same day, colonic stenting was performed to relieve the symptoms of stenosis. After 1 month of stenting, a robot-assisted laparoscopic sigmoid colectomy and left lateral lymph node dissection were performed. Postoperative pathological examination revealed regional lymph node metastasis and left lateral lymph node metastasis(#283); the patient was diagnosed with pT4aN1bM1a(LYM), fStage Ⅳa. The patient was discharged on postoperative day 10, and is stable 5 months after surgery without recurrence. This case suggests that robot-assisted laparoscopic lateral lymph node dissection can be effective even in atypical cases of sigmoid colon cancer with lateral lymph node metastasis.

[Treatment Strategy for Stage â £ Rectal Cancer Considering Local Treatment Outcomes].

We investigated 36 patients with Stage Ⅳ rectal cancer who underwent primary resection in our department between November 2015 and June 2020. Tumor localization was upper in 20 cases and lower in 16 cases. Six patients had the cT4b stage at initial diagnosis, and lateral lymph node metastases were detected in 6 cases. Preoperative treatment consisted of doublet chemotherapy in 20 cases, in combination with bevacizumab in 17 cases. Surgery for distant metastases was performed in 21 patients, and the final results were curative(Cur B)in 20 patients and palliative(Cur C)in 16 patients. Perioperative mortality was observed only in Cur C patients(5.6%). The local R1 resection rates in Cur B and Cur C patients were 10.0% and 18.8%, respectively, and the corresponding local RM≤1 mm rates were 55.0% and 43.8%. Additionally, the local recurrence rates were 25.0% and 0%, and the 3-year OS rates were 80.9% and 25.5%, respectively, in Cur B and Cur C patients. In Cur B, the local RM≤1 mm rates in the preoperative and non-preoperative treatment groups were 38.5% and 85.7%, respectively, and the corresponding local R1 resection rates were 7.7% and 14.3%. Additionally, the 3-year local recurrence-free survival rates were 68.2% and 66.7% and the 3-year OS rates were 82.1% and 80.0%, respectively, in the preoperative and non-preoperative treatment groups. We determined that preoperative chemotherapy alone is not sufficient for the local treatment of Stage Ⅳ rectal cancer, and concomitant preoperative radiotherapy should be considered. The prognosis of patients with Cur C is poor, and surgery-related deaths have been observed, which can be a problem for the palliative resection strategy.

[Intrathoracic Migration of a Kirschner Wire Successfully Removed by Video-assisted Thoracic Surgery:Report of a Case].

A 40-year-old man who had been surgically treated for the fracture of the right humerus with two Kirschner wires (K-wires) complained of chest pain and difficulty in breathing at fourth day after surgery and visited our hospital. Chest radiography revealed dislocation of the K-wire and right pneumothorax. Video-assisted thoracic surgery( VATS) was performed immediately, and the K-wire was removed safely.

[Two Cases in Which Simultaneous Laparoscopic Surgery and Breast Cancer Surgery Using a Head-Mounted Monitor Were Useful].

Herein, we report on how we were able to reduce the operation time by simultaneously performing laparoscopic surgery and breast cancer surgery using a head-mounted monitor(HMS-3000MT, Sony corporation). Case 1: 60s, female. A 5.5 cm leiomyoma was found in the central thoracic esophagus, and a 1 cm breast cancer was found in the C region of the left mammary gland. Subtotal esophagectomy with right thoracotomy and laparoscopy and a left partial mastectomy were performed. For the abdominal surgery, HMS-3000MT was used under hand-assisted laparoscopy, and a left partial mastectomy was performed concurrently. Operation time was 367 minutes(simultaneous surgery for 56 minutes). Esophagus: leiomyoma, 50×45 mm; and mammary gland: 16×15 mm, pTis(DCIS), pN0(sn), cM0, and pStage 0. Case 2: 70s, female. A 3 cm sized GIST was found on the posterior wall of the middle gastric body, and a breast cancer of 1.3 cm was also found in the B region of the right mammary gland. Using HMS-3000MT, laparoscopic local resection of the stomach and right total glandectomy were performed concurrently. Operation time was 114 minutes(simultaneous surgery for 58 minutes). Stomach: GIST, 25×22 mm, and modified Flecher classification low risk; and mammary gland: invasive ductal carcinoma, 15×15 mm, pT1c, pN0(sn), cM0, and pStage Ⅰ. Conclusion: In 2 fields of surgery, simultaneous surgery using HMS-3000MT was considered to be a useful method to shorten the operation time.

[Short-Term Results of Robot-Assisted Surgery in Patients Undergoing Neoadjuvant Chemotherapy for Rectal Cancer].

The advantages of robot-assisted surgery include: stable deployment of the robotic arm that enables excellent radical cure characteristics and preservation of function; the ability to perform precise surgery even in patients in whom performing laparoscopic surgery is difficult, such as those with pelvic or bulky tumors. However, there have been some reports on such issues as an increase in the incidence of postoperative complications and an increase in postoperative hospital stay in patients who underwent neoadjuvant chemotherapy(NAC); thus, we summarized and are reporting the short-term results of our experience in patients seen in our department to date. A total of 76 patients with rectal cancer who underwent robot-assisted surgery, and short-term postoperative results were compared between patients who underwent neoadjuvant chemotherapy (NAC group)and those who did not undergo neoadjuvant chemotherapy(non-NAC group). Of the 76 patients, 59 (77.6%)were male and 17(22.4%)were female, and 27(35.5%)in the NAC group. In the comparisons between the NAC and non-NAC groups, although the difference in operative time(523.5 vs 317.5 minutes, p<0.01)was significant, there were no significant differences in any of blood loss(59 vs 20g, p=0.22), postoperative hospital stay(14 vs 13 days: p=0.07), and onset of complications that were Clavien-Dindo Grade Ⅲa or higher(2 vs 1 patients, p=0.82). Robot- assisted surgery after NAC for rectal cancer was considered to be safe and very useful.

The Cell Line-Dependent Diversity in Initial Morphological Dynamics of Pancreatic Cancer Cell Peritoneal Metastasis Visualized by an Artificial Human Peritoneal Model.

BACKGROUND: Pancreatic ductal adenocarcinoma is considered as one of the most malignant types of cancer with rapid metastasis and invasion of the cancer cells, having peritoneal metastasis (PM) as a dominant factor of poor prognosis. Although the prevention of peritoneal dissemination would result in the inhibition of the initial metastatic process and contribute in improving the poor prognosis of the pancreatic cancer, the initial dynamics of PM are still unclear because of the lack of adequate models in studying the morphological and molecular details of pancreatic cancer cells. MATERIALS AND METHODS: The artificial human peritoneal tissue (AHPT) that can be applied in studying for the spatial dynamics of cancer PM in vitro has been established previously. In this study, the initial dynamics of the three pancreatic cell lines, undifferentiated carcinoma MIA PaCa-2, poorly differentiated adenocarcinoma Panc-1, and moderately differentiated adenocarcinoma BxPC3 on AHPT are examined. RESULTS: In a morphological analysis using light and electron microscopy, MIA PaCa-2 cells spread on the mesothelial layer with disruption of the sheet structure and infiltrated into the stroma-like tissue in AHPT. On the other hand, BxPC3 cells changed shapes from round into flat ones with rapid proliferation and formed sheet structure at the surface of the tissue replacing the mesothelial layer without vertical invasion into the tissue. Panc-1 cells demonstrated the intermediate characteristics of MIA PaCa-2 and BxPC3 on AHPT. These diverse morphological characteristics were verified by the correspondence with the results in a mouse model and were reflected by the profile of secreted oncogenic proteins of the three pancreatic cell lines. CONCLUSIONS: The initial dynamics in the peritoneal dissemination of these pancreatic cancer cell lines were demonstrated by AHPT, showing the morphological and molecular diversity depending on the degree of differentiation or the properties of oncogenic protein secretion.

Short-term outcomes of robotic-assisted laparoscopic versus laparoscopic lateral lymph node dissection for advanced lower rectal cancer.

BACKGROUND: Therapeutic strategies to suppress local recurrence, including lateral lymph node metastasis, are important to improve the curability of rectal cancer. The aim of the present study was to clarify the advantages of robotic-assisted laparoscopic lateral lymph node dissection (RALLD), comparing its short-term outcomes with those of laparoscopic lateral lymph node dissection (LLLD). There are some retrospective reports comparing RALLD or LLLD and open lateral lymph node dissection (OLLD), but few reports comparing RALLD and LLND to each other. METHODS: From November 2014 to August 2020, we compared the short-term outcomes in 40 patients who underwent RALLD and 55 patients who underwent LLLD. RESULTS: The total operative time was significantly longer in the RALLD group than in the LLLD group (p < 0.001). However, lateral dissection time was not significantly different between the groups (p = 0.661). The postoperative hospital time was shorter in the RALLD group than in the LLLD group (p < 0.048). No significant differences were identified in the rates of postoperative bleeding, incisional surgical site infection (SSI), organ/space SSI, urinary disfunction, urinary infection, or small bowel obstruction between the groups. However, anastomotic leakage was significantly lower in the RALLD group than in the LLLD group (p = 0.031). CONCLUSIONS: The short-term outcomes of RALLD indicate it is feasible, and RALLD may be a useful modality for lower rectal cancer.

[A Case of Laparoscopic Distal Gastrectomy for Gastric Cancer with an Adachi Type â ¥ Group 24 Vascular Anomaly].

We report a case of successful laparoscopic distal gastrectomy for gastric cancer with an Adachi type Ⅵ group 24 vascular anomaly. A male in his 60s exhibited a type 0-Ⅱa plus Ⅱc lesion at the lesser curvature of the gastric angle by esophagogastroduodenoscopy and was diagnosed with tub2. He was referred to us for surgical treatment. The clinical diagnosis was cT1bN0M0, and cStage Ⅰ. Preoperative multidetector-row computed tomography(MDCT)showed an Adachi type Ⅵ group 24 vascular anomaly. At laparoscopic surgery, we dissected No. 8a lymph nodes with exposure of the surface of the portal vein because the common hepatic artery was absent. The left gastric artery and splenic artery formed a common trunk. As there are various kinds of vascular anomalies of the celiac artery branch, we must understand the arterial running pattern prior to gastric surgery. This technique is more useful in laparoscopic surgeries where tactile sensation is limited. To prevent perioperative and postoperative complications, we must recognize the anomaly pattern prior to surgery using MDCT.

[A Successfully Treated Patient Who Underwent Esophageal Bypass Surgery after Undergoing Stent Placement for Unresectable Advanced Esophageal Cancer Stenosed after CRT].

Esophageal bypass surgery is a treatment for oral ingestion in cases of unresectable esophageal cancer with esophageal stricture. Esophageal bypass surgery may be necessary especially in cases of advanced esophageal stricture after CRT because of the high risk of bleeding and perforation due to esophageal stent placement. In recent years, as a safe technique with fewer complications, esophageal bypass surgery using a Y-shaped gastric tube has been increasingly performed. Therefore, we will introduce cases that have undergone esophageal bypass surgery after undergoing stent placement for unresectable advanced esophageal cancer stenosed after CRT.

[A Case in Which Trastuzumab Combined Chemotherapy Was Effective for Recurrence of Post-Operative Gastric Cancer with Partial HER2 Overexpression].

We report a case in which recurrent partial HER2-positive gastric cancer showed complete clinical response to capecitabine (Cape)/oxaliplatin(L-OHP/OX)(CapeOX)plus trastuzumab(Tmab)combined chemotherapy for 32months. A 65-yearold man underwent distal gastrectomy, D2 lymph node dissection, and Roux-en-Y reconstruction for type 2 gastric cancer of the prepyloric anterior wall in December 2014. Pathological stage was as follows: L, ant, Type 2, 32×22 mm, tub1>tub2> por1, pT2(MP), int>med, INF c>a, Ly1a, V0, pN0, cM0, cH0, cP0, pCY0, pStage I B, pPM0(60mm), pDM0(75mm), pR0. Immunostaining of the tumor indicated overexpression of the HER2 gene in more than 10% of the well differentiated tubular adenocarcinoma(tub1). Nineteen months post-surgery, pancreatic head lymph node metastasis was diagnosed, and we started CapeOX plus Tmab combined chemotherapy. After 19 courses, the metastatic lymph node reduced its size until we could not detect it on CT. We continued treatment for 45 courses(about 32 months). During the courses, there were adverse events such as peripheral neuropathy(Grade 3, CTCAE v5.0), which required interruption of L-OHP, and oral mucosal ulcer (Grade 2).

Smoking cessation contributes to weight gain in patients with hepatobiliopancreatic malignancy.

BACKGROUND & AIMS: The relationship between smoking cessation and weight gain is well recognized. However, there is no data currently available on the effect of smoking cessation on weight gain in patients with malignancy. The aim of this study was to clarify the body weight (BW) change after smoking cessation in patients with malignancy. METHODS: We retrospectively analyzed 159 subjects who underwent hepatobiliopancreatic surgery. The smoking status was determined using questionnaires administered at the initial presentation, and the candidates were divided into two groups: recent quitters and nonsmokers. The change in the BW was compared between these two groups. RESULTS: There were 134 subjects with malignant disease (84.3%), with a median age of 68 (range: 26-84) years. In the nonsmoker group, 28 of 116 subjects (24.1%) gained weight between the initial presentation and admission. In the recent quitter group, 12 of 18 subjects (66.7%) gained weight in the same period (P < 0.01). Regarding the change in the BW from the initial presentation, recent quitters gained more weight than nonsmokers (+1.7 kg [+2.7%] vs. -1.0 kg [-2.0%], P < 0.01). Furthermore, the improvement from the initial presentation was seen in a higher percentage of recent quitters than nonsmokers with respect to Onodera's prognostic nutritional index (61.1% vs. 36.2%, P = 0.04) and the controlling nutritional status score (38.9% vs. 19.3%, P = 0.07). CONCLUSIONS: Weight gain due to smoking cessation was observed even in patients with hepatobiliopancreatic malignancy.

Microanatomical profiles on the lymphatic system in the human ampulla of Vater (immunohistochemistry and scanning electron microscopy).

BACKGROUND: Little information is available regarding microanatomy of lymphatic system in the ampulla of Vater, though it is of critical importance for an understanding of tumor progression via the lymphatics and determination of surgical strategy. The present study, therefore, aimed to demonstrate the distribution and microanatomical profiles on the lymphatic system in the ampulla. METHODS: The fine distribution and structure of the lymphatic vessels were investigated in the ampulla and the stomach by immunohistochemistry for lymphatic- (D2-40) and blood vascular- (CD31) specific markers and scanning electron microscopy. The densities of lymphatic and blood vessels were also compared. RESULTS: The duodenal papilla densely developed the lymphatics with distinct aspects of lymphatic capillaries, together with blood vessels. The density of lymphatic capillaries in the extramuscular layer in the ampulla was higher than those of both the other ampullary layers and the gastric extramuscular (subserosal) layer. CONCLUSIONS: The ampulla of Vater showed widespread lymphatic capillaries throughout the entire wall. The specific vascular system is suited to produce lymph everywhere and drain without via such a large vessel as lymphatic collector. This suggests that tumor cells invade the lymphatics and metastasize more easily in the ampulla than in the other gastrointestinal regions.