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 outcomes of robotic-assisted surgery following neoadjuvant chemotherapy for lower rectal cancer.

INTRODUCTION: There have been reports about robotic surgery for rectal cancer with chemoradiotherapy (CRT), but only a few studies have compared the use of robotic surgery with and without neoadjuvant chemotherapy (NAC). The aim of our study was to compare the perioperative outcomes of robotic surgery with and without NAC for lower rectal cancer and to examine the effects of NAC on robotic surgery. METHODS: From January 2016 to July 2021, we compared the short-term outcomes of 45 patients who did not undergo NAC and 55 patients who underwent NAC. RESULTS: The rate of sphincter-preserving surgeries was higher in the NAC group than in the non-NAC group (P = .024). The total operative time was significantly longer in the NAC group than in the non-NAC group (P < .001). The rate of lateral lymph node dissection was significantly higher in the NAC group than in the non-NAC group (P < .001). No significant differences were identified in the rate of incisional surgical site infections (SSI), organ/space SSI postoperative bleeding, small bowel obstruction, anastomotic leakage, urinary dysfunction, or urinary infections between the groups. There were eight incidences of lateral lymph node metastasis (15%) and two cases with positive resection margins (4.0%) in the NAC group. CONCLUSIONS: Robotic surgery after NAC has few complications and a higher sphincter-preserving rate that without NAC.

[A Case of Descending Colon and Rectal Cancer with Acute Myeloid Leukemia Performed Robot‒Assisted Hartmann's Procedure].

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. A second course of CAG therapy was started 15 days postoperatively. However, he was then diagnosed with exacerbation of the AML; remission induction therapy (daunorubicin, cytarabine)was started in November. In December, he developed a fever and abdominal pain, and on CT scan, it was discovered that an abscess had formed around the rectal resection site. Myelosuppression from AML led to prolonged sepsis; and by January 2020, the sepsis was systemic. His actual cause of death was given as circulatory failure. We report this, because only a few cases on the treatment of overlapping AML and colorectal cancers can be found in the literature.

Widespread anorectal lymphovascular networks and tissue drainage: analyses from submucosal India ink injection and indocyanine green fluorescence imaging.

AIM: Abdominoperineal resection is associated with poor prognosis in patients with advanced lower rectal cancer. This study aimed to analyse the functional lymphovascular network and tissue drainage in the anorectal region. METHODS: In this descriptive study, we performed microanatomical evaluations and intra-operative imaging analysis in a cadaver and patients with rectal cancer. Specimens with India ink injection were collected from a cadaver and from six patients who underwent abdominoperineal resection. Intra-operative indocyanine green fluorescence imaging was performed on four patients who underwent surgery for lower rectal cancer. India ink was injected into the submucosa at the dentate line of specimens. Tissue sections were examined by immunohistochemistry for D2-40 and CD31. Intra-operative indocyanine green was injected into the submucosa at the dentate line. Lymph flow was traced using a near-infrared camera system. RESULTS: Fascia branching from the rectal longitudinal muscle layer extended to the posterior hiatal ligament and lateral endopelvic fascia connective tissue lamina on the surface of the levator ani muscle. The fascia contained veins labelled with ink in their lumina and initial lymphatics. Intra-operative indocyanine green fluorescence imaging revealed extensive lymph flow from the muscle layer of the anal canal to the hiatal ligament and endopelvic fascia along the longitudinal muscle layer fibres. CONCLUSIONS: The anorectal region contained widespread venous and lymphatic networks in proportion to its specific connective tissue framework around the longitudinal-muscle-layer-extending muscle bundles, which provides extensive networks for tissue fluid and cells.

[A Case of Myocardial Metastasis of Esophageal Squamous Cell Carcinoma].

Myocardial metastasis for esophageal squamous cell carcinoma(ESCC)is relatively rare and it is diagnosed as a part of widespread metastasis in the terminal stage. We experienced a case of myocardial metastasis of ESCC treated effectively with chemoradiotherapy. A 56-year-old man was diagnosed ESCC(clinical T3N2M0, Stage III). He received neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin followed by subtotal esophagectomy with dissection of the 3 regional lymph nodes. The pathological diagnosis was moderate differentiated squamous cell carcinoma, CT-pT3(T3), pN1, sM0, fStage III. Four months after surgery, he had no clinical symptom, however myocardial metastasis located in the apex was detected on the follow up positron emission tomography(PET). Chemoradiotherapy was performed for the myocardial metastasis. Myocardial metastasis treated effectively with chemoradiotherapy almost disappeared on the PET and computed tomography taken 3 months after chemoradiotherapy. He died, however, of multiple liver and bone metastases 15 months after the initial surgery.

[A Case of Advanced Gastric Cancer with Peritoneal Dissemination after Gastrectomy Effectively Treated with Combination Chemotherapy of Ramucirumab and Paclitaxel].

The REGARD and RAINBOW trials revealed the effectiveness of ramucirumab(RAM)for advanced gastric cancer patients who had been previously treated with chemotherapy. In the latest Japanese gastric cancer treatment guidelines, PAM plus paclitaxel(PTX)was positioned as a second-line chemotherapy for advanced gastric cancer. We report a case of advanced gastric cancer with peritoneal dissemination after gastrectomy effectively treated with RAM plus PTX. A 66-year-old woman underwent total gastrectomy with D2 lymph node dissection, splenectomy, and distal pancreatectomy. The pathological diagnosis was poorly differentiated adenocarcinoma, pT4b(pancreas), N3b, P1, CY1, Stage Ⅳ. She was treated with postoperative chemotherapy of S-1 plus cisplatin. However, 5 months after surgery, computed tomography(CT)showed ascites and recurrence of peritoneal dissemination. Cytological examination showed adenocarcinoma cells in the ascites. She was treated with combination chemotherapy of RAM and PTX as second line chemotherapy. After 1 course of this therapy, CT revealed complete disappearance of ascites and significant reduction in the size of the peritoneal dissemination. The patient survived without progression for 8 months after the recurrence was detected.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

[A Case of Perforated Gastric Cancer Treated with Curative Resection Following Conservative Medical Management and Chemotherapy].

Perforated gastric cancer typically requires life-saving emergency surgery. However, preoperative diagnosis is difficult, the rate of radical resection is low, and the prognosis remains poor. Perforated gastric cancer is generally treated with 1- or 2- stage gastrectomy, but radical resection is rarely performed after a conservative medical management and chemotherapy for perforated gastric cancer. A 65-year-old man visited another hospital with left upper abdominal pain. He was diagnosed with upper GI perforation, and conservative medical management was selected because peritonitis was limited. After close examination, a Type 3 tumor was found in the cardiac region of the stomach. As the advanced gastric cancer was unresectable, chemotherapy, comprising4 courses of SP plus T-mab, was subsequently administered. As the therapeutic effect was PR, we performed total gastrectomy. The pathological findings were tub2>tub1>por2: pT2N1CY0H0P0M0, pStageⅡ, and we achieved curative resection. Postoperatively, S-1 treatment was performed as an adjuvant chemotherapy. The patient remains alive, without recurrence, for 3 years and 6 months postoperatively.

[A Case of Laparoscopic Resection for Locally Advanced Primary Rectal Cancer after Neoadjuvant Chemotherapy].

We treateda 70-year-oldfemale patient with locally advancedrectal cancer accompaniedby metastases to other organs. Three courses of S-1 plus oxaliplatin(SOX)therapy were administered as neoadjuvant chemotherapy(NAC), andthe cancer was subsequently treatedwith laparoscopic rectal resection. She hadvisiteda physician with a chief complaint of melena. A type 2 tumor located in the rectum Rb was found during the lower gastrointestinal endoscopy, which was diagnosed as an adenocarcinoma by biopsy. Vaginal invasion andlymph node metastasis were observedon CT andMRI. After 3 courses of SOX therapy(NAC), her condition was categorized as SD. Laparoscopic rectal amputation(D3)combinedwith resection of the ovary, uterus, and vagina was performed. On histopathological examination, the tumor was an adenocarcinoma, muc> tub2, ypT4b(AI, vaginal wall), int, INF b, ly1, v2, EX(-), PN1a, grade 1, pPM0, pDM0, pRM0 and pStage Ⅲa. The histological analysis demonstrated that the therapeutic effect of chemotherapy was grade 1a. Laparoscopic surgery, which is a relatively safe procedure, may be useful after NAC for an R0 resection.

[The Impact of Neutrophil-Lymphocyte Ratio on the Prognosis in Patients Who Underwent Esophagectomy for Esophageal Cancer].

BACKGROUND: Thene utrophil-lymphocyteratio (NLR)reflects a patient's systemic inflammatory response. Several studies have revealed that the NLR is associated with a poor prognosis in several types of malignant tumors such as colorectal and lung cancer. The aim of this study was to evaluate the impact of preoperative NLR on the prognosis of patients with esophageal cancer. METHODS: The NLR was calculated for 93 consecutive patients with clinical Stage II or III esophageal cancer, who underwent curative esophagectomy following neoadjuvant chemotherapy between 2011 and 2013. The impact of preoperativeNLR on overall survival(OS)after esophagectomy was evaluated. The NLR cut off value was set to 2. RESULTS: The 3-year OS of patients with NLR≥2 was significantly shorter than patients with NLR<2(40.5% vs 67.9%, p=0.005). In a multivariateCox model, NLR≥2(HR: 2.342, 95%CI: 1.095-5.007, p=0.028), pathological depth of tumor(HR: 3.207, 95%CI: 1.114- 9.233, p=0.031), and an ageove r 60(HR: 2.342, 95%CI: 1.117-6.501, p=0.027)were identified as independent prognostic factors for OS after esophagectomy. CONCLUSIONS: The preoperative NLR was significantly associated with a poor prognosis in esophageal cancer patients who underwent curative esophagectomy following neoadjuvant chemotherapy.

[Cystic Duct Cancer with Postoperative Liver Metastasis That Achieved Complete Response after Gemcitabine Treatment - A Case Report].

A 72-year-old woman was diagnosed with gallbladder cancer and underwent extended cholecystectomy and extrahepatic bile duct resection. The pathological findings were CGnBdGb, circ, nodular infiltrating type, 20×10 mm, tub2, pT3b, int, INF c, ly1, v1, ne3, pN0, pDM0, pHM0, pEM0, pPV0, pA0, R0, Stage III A. Because the main localization was in the cystic duct, we diagnosed this as cystic duct cancer. Seven months after surgery, follow-up computed tomography scan revealed a metastatic region in segment 7 of the liver. She underwent chemotherapy with gemcitabine(GEM). After 3 courses of GEM, the metastatic lesion became obscure. After 8 courses, the metastatic lesion disappeared, and the patient showed complete response. We discontinued chemotherapy after 21courses of GEM, and the patient is alive with no signs of recurrence 4 years and 4 months after surgery.

[A Case of Double Cancer of Initially Unresectable Sigmoid Colon Cancer and Advanced Gastric Cancer Treated with Curative Resection after mFOLFOX6 Therapy].

A 61-year-old man was admitted to our hospital because of a complaint of blood in stool. He was diagnosed with advanced colon and gastric cancers. Computed tomography (CT) revealed a sigmoid tumor with invasion to the bladder, a metastatic tumor in the lateral segmental branch of the left hepatic lobe, and ascites. He was diagnosed with initially unresectable double cancer. Ileostomy was performed immediately, and he was treated with modified (m) FOLFOX6 regimen (oxaliplatin in combination with infusional 5-fluorouracil/Leucovorin). After 6 courses of the mFOLFOX6 regimen, CT revealed that the primary lesion of the sigmoid colon and liver metastasis had reduced in size, and the ascites had disappeared. Gastroscopy revealed that the gastric cancer had disappeared. Biopsy results were negative. Accordingly, his gastric cancer was diagnosed as treatment effect Grade 3. After 8 courses of mFOLFOX6 therapy, sigmoidectomy, partial resection of the bladder, and partial resection of the liver were performed. Gastric cancer was not resected in accordance with his will. Although 40 months has passed after the radical resection, neither the sigmoid colon cancer nor the gastric cancer recurred.

[A Case of Neuroendocrine Carcinoma of the Esophagus Treated with Neoadjuvant Chemotherapy Comprising 5-Fluorouracil plus Cisplatin].

Esophageal neuroendocrine carcinoma is relatively rare and the prognosis is poor owing to its aggressive malignancy. We experienced a case of neuroendocrine carcinoma of the esophagus treated with neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin. A 71-year-old man was diagnosed with esophageal carcinoma(clinical T3N1M0, Stage III ). He received neoadjuvant chemotherapy comprising 5-fluorouracil plus cisplatin, followed by subtotal esophagectomy with dissection of 3 regional lymph nodes. Immunohistochemical findings were synaptophysin-positive, CD56-positive, Ki-67(labeling index) B90%. The final diagnosis was neuroendocrine carcinoma, categorized as CT-pT1a-MM, pN0, Stage 0. The pathological response to neoadjuvant chemotherapy was Grade 2. The patient is alive 8 months after esophagectomy without metastasis.