Phase II trial evaluating the long-term efficacy and peripheral sensory neuropathy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer.

Adjuvant oxaliplatin plus capecitabine (XELOX) therapy is recommended for patients with curatively resected colon cancer. However, prospective data on its practical application in Japanese patients are limited. Therefore, we aimed to conduct a long-term clinical evaluation of the efficacy and safety of adjuvant XELOX in patients with curatively resected stage III colon cancer (MCSCO-1024). This prospective, multi-center, open-label, single-arm, phase II study enrolled patients with curatively resected stage III colon cancer. The treatment protocol consisted of a 120-minute intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and two divided doses oral capecitabine (2000 mg/m2/day) for 14 days in a 3-week cycle, totaling eight cycles (24 weeks). The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 5-year overall survival and long-term prognosis of peripheral sensory neuropathy. A total of 196 patients were enrolled between November 2011 and August 2014 (34 months). The 3-year DFS rate was 73%, and the 5-year overall survival rate was 87%. The overall incidence of peripheral sensory neuropathy was 17%, with a 1% rate of grade 3 neuropathy after 5 years. Adjuvant XELOX demonstrated utility and safety in the clinical management of Japanese patients with stage III colon cancer.

Safety and short-term outcomes of robotic-assisted transabdominal preperitoneal repair for inguinal hernia in pioneering hospitals in Japan: A nationwide retrospective cohort study.

INTRODUCTION: We aimed to evaluate the safety and short-term outcomes of robotic-assisted transabdominal preperitoneal repair for inguinal hernia in 12 pioneering hospitals in Japan. METHODS: Clinical data of patients who underwent robotic-assisted transabdominal preperitoneal repair between September 1, 2016, and December 31, 2021 were collected. Primary outcome measures were intra-operative adverse events and post-operative complications, whereas secondary outcomes were surgical outcomes, including chronic pain, recurrence, and learning curve. RESULTS: In total, 307 patients were included. One case of inferior epigastric arterial injury was reported; no cases of bowel or bladder injury were reported. Thirty-five seromas were observed, including four (1.3%) cases that required aspiration. The median operative time of a unilateral case was 108 minutes (interquartile range: 89.8-125.5), and post-operative pain was rated 1 (interquartile range: 0-2) on the numerical rating scale. In complicated cases, such as recurrent inguinal hernias and robotic-assisted radical prostatectomy-associated hernias, dissection and suture were safely achieved, and no complications were observed, except for non-symptomatic seroma. All patients underwent robotic procedures, and there was no chronic post-operative inguinal pain, although one case of hernia recurrence was reported. Regarding the learning curve, plateau performance was achieved after 7-10 cases in terms of operative time (P < .001). CONCLUSION: Robotic-assisted transabdominal preperitoneal repair can be safely introduced in Japan. Regardless of the involvement of many surgeons, the mastery of robotic techniques was achieved relatively quickly. The advantage of robotic technology such as wristed instruments may expand the application of minimally invasive hernia repair for complicated cases.

Clinical Significance of Increased Skeletal Muscle Mass During Nab-Paclitaxel Plus Gemcitabine Treatment in Patients With Advanced Pancreatic Cancer.

OBJECTIVES: The clinical significance of increased skeletal muscle mass during nab-paclitaxel plus gemcitabine (AG) treatment in patients with advanced pancreatic cancer (APC) remains unknown. Therefore, we retrospectively investigated the characteristics of patients after AG treatment to evaluate the clinical significance of increased skeletal muscle mass during treatment. METHODS: From January 2015 to August 2021, 67 patients with APC received AG as first-line chemotherapy at Higashiosaka City Medical Center. Of these patients, 39 received second-line (2L) chemotherapy after AG therapy, and 28 received best supportive care. Patients' characteristics at the end of AG treatment were compared retrospectively between these 2 groups, and the relevant factors at the end of first-line treatment for 2L chemotherapy induction were analyzed. RESULTS: A performance status of 0 to 1 and increased skeletal muscle mass during AG therapy were independently associated with 2L chemotherapy induction in multivariate analysis. A high relative dose intensity (≥50%) in the first 8 weeks of AG treatment was more frequently found in patients with increased skeletal muscle mass during treatment ( P = 0.037). CONCLUSIONS: Increased skeletal muscle mass during AG treatment might contribute to the higher prevalence of 2L chemotherapy induction in patients with APC.

[A Case of Laparoscopic Uterine and Vaginal Resection for Local Recurrence after Abdominoperineal Resection for Anal Canal Cancer].

The patient was an 80s woman. She visited our hospital with chief complaint of melena, and further evaluation revealed anal canal cancer. We performed robot-assisted abdominoperineal resection(D3 lymphadenectomy)and lateral lymph node dissection. The pathological diagnosis was anal canal cancer, muc>por1>tub2, T3N1bM0, pStage Ⅲb. One year after the surgery, she had a mass in the soft tissue of perineum on CT scan and PET-CT showed abnormal accumulation, which was diagnosed as local recurrence. At the same time, she also had a mass with abnormal accumulation in ascending colon, and it was diagnosed as ascending colon cancer. In both cases, we judged radical resection was possible, and the policy of surgery was decided. First, laparoscopic ileocecal resection was performed. The local recurrence lesion became a mass, invading the soft tissue of the perineum, the posterior wall of the vagina, and the cervix. So, we performed laparoscopic excision of local recurrent region together with the uterus and the posterior wall of the vagina. Based on the result of pathological examination, the patient was diagnosed with ascending colon cancer(tub1, pT1bN1aM0, pStage Ⅲa), and recurrence of anal canal cancer. The postoperative course is good and there are no signs of recurrence for 6 months after the operation.

Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer.

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.

Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer.

OBJECTIVE: Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS: Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS: Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS: Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.

[A Case of Robotic-Assisted Total Pelvic Exenteration for Locally Advanced Rectal Cancer Invading the Prostate].

The patient was a 60s man, whose chief complaint of melena and weight loss. He visited our hospital, and further evaluation revealed rectal cancer(Rb)invading the prostate with obturator lymph node metastasis. The clinical diagnosis was T4b (prostate)N3M0, Stage Ⅲc. He was administered 4 courses of CAPOX plus bevacizumab. After chemotherapy the primary tumor and lymph nodes showed PR, the diagnosis of ycT4bN1bM0, Stage Ⅲc. We performed robot-assisted total pelvic exenteration. He has been cancer-free for 5 months.

[A Case of Laparoscopic Total Pelvic Exenteration for Sigmoid Colon Cancer Using Infrared Illumination System (IRIS)].

The patient was 80s woman, whose chief complaint of fever and abdominal pain. She visited our hospital, and further evaluation revealed sigmoid colon cancer invading the uterus and abdominal wall. The pooling of pus in the uterus was formed and we diagnosed as pyometra. The clinical diagnosis was T4b(uterus, abdominal wall)N0M0, cStage Ⅱc. We performed laparoscopic sigmoidectomy, uterus and bilateral ovaries. We report a case in which the intraoperative infrared illumination system(IRIS)was used to support the identification of the ureter by near-infrared light and total pelvic exenteration could be safely performed.

Impact of aspirin discontinuation on thrombotic complications in laparoscopic colorectal cancer surgery.

BACKGROUND: The number of patients taking antiplatelet therapy is increasing. However, there is no definitive guideline for the perioperative management of antiplatelet therapy. Conventionally, the discontinuation of antiplatelet drugs has been the basic treatment as perioperative management. Therefore, we investigated the risk of discontinuing aspirin concerning thrombotic complications in laparoscopic colorectal cancer surgery. METHODS: Between January 2015 and December 2019, a total of 729 patients underwent laparoscopic colorectal cancer surgery in Toyonaka Municipal Hospital. Sixty-four patients taking antithrombotic drugs aside from aspirin were excluded from this study; the remaining 665 patients were considered eligible and divided into three groups. The patients not taking aspirin were classified as the "Control group" (n = 588). Among the patients taking aspirin, those who continued preoperative aspirin were classified as the "Aspirin group" (n = 30), and those who discontinued preoperative aspirin were classified as the "No-aspirin group" (n = 47). The Aspirin, No-aspirin, and Control groups were compared retrospectively. RESULT: Among the 3 groups, there were no significant difference in operative time (p = 0.14), bleeding volume (p = 0.63), or postoperative hospital stay (p = 0.06). Assessing the postoperative complication, bleeding complications were significantly more frequent in the Aspirin group (p < 0.01), although those complications were all Clavien-Dindo grade II. In contrast, thrombotic complications were significantly more frequent in the No-aspirin group (p < 0.01). Note that those complications were all Clavien-Dindo Grade III/IV. This result suggested that discontinuing aspirin increased the risk of severe thrombotic complication. CONCLUSION: Discontinuation of aspirin as perioperative management in laparoscopic colorectal cancer surgery increased the risk of severe thrombotic complications.

[A Case of Early Appendiceal Adenocarcinoma Coexisting with High-Grade Appendiceal Mucinous Neoplasm].

We report a case of a female in her fifties with early appendiceal adenocarcinoma coexisting with high-grade appendiceal mucinous neoplasm(HAMN)with a review of the literature. The patient presented to our hospital because of an enlarged appendix noted by contrast-enhanced CT performed for hematuria. Contrast-enhanced CT showed that the appendix had swollen to 10 mm and mucus had accumulated inside, which had no evidence of obvious malignancy. She was followed up on CT once a year. Four years after her first visit, she underwent laparoscopic appendectomy for a definitive diagnosis. There were no adhesions or inflammation in her abdominal cavity, and the appendix root was dissected with an automatic anastomosis device. Her resected specimen macroscopically showed mild wall thickening, but no obvious neoplastic lesion. Pathological examination revealed that in many areas centered on the tip of the appendix, highly columnar atypical epithelium with enhanced mucus production was densely proliferated in the form of glandular tubular and papillary. The nuclei of the proliferating epithelium were large and the fission image was conspicuous, but they remained in the mucosa. Pathological examination diagnosed as HAMN according to the WHO classification. The atypical epithelium in a small area at the tip was particularly strong in nuclear atypia, and showed a strong positive diffusely in p53, which was an image of well-differentiated tubular adenocarcinoma. The pathological diagnosis was V, Type 0-Ⅱb, 2 mm, tub1 in HAMN, pTis, Ly0, V0, Pn0, pPM0, pDM0, pRM0, R0. Six months have passed since the operation, but no recurrence has been observed.

[A Case of Anastomotic Recurrent Descending Colon Cancer Successfully Treated with Single-Incision Laparoscopic Partial Colectomy with Intracorporeal Anastomosis].

A 60s-year-old male, who had laparoscopic partial colectomy with resection of left colic artery for descending colon cancer 8 years ago and completed 5-year-follow-up without the evidence of recurrence, was diagnosed as anastomotic recurrence of descending colon cancer, and referred to our hospital. We planned and safely performed single-incision laparoscopic colectomy(SILC)with intracorporeal anastomosis(ICA)(operation time of 390 min and estimated blood loss of 60 g). Following the adhesiolysis, the intracorporeal resection of the lesion was performed with automatic stapling device preserving middle colic and inferior mesenteric arteries and veins. Then, after the recovery of the specimen, ICA was performed as follows; after making a small hole just below the staple line at the opposite side of mesenteric attachment, the oral and the anal stump of colon was pulled-up and placed side-by-side with temporary strings and automatic suturing device was inserted into the holes and fired to form a side-to-side anastomosis, then the common stab incision was pulled- up with 3 temporary strings and closed with a stapler. The postoperative course was smooth and discharged on postoperative day 8. The ICA can be a good option for SILC when colonic and vascular tension would be the limiting factor of anastomosis.

The Validity of a New Edition of Classification for Ovarian Metastasis from Colorectal Cancer.

OBJECTIVES: In the 9th edition of the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma (JCCRC), ovarian metastasis is classified as distant metastasis. We assessed the significance of resection of ovarian metastases and the validity of this 9th edition of JCCRC for ovarian metastases from colorectal cancer (CRC). METHODS: We retrospectively analyzed the clinicopathological factors and overall survival of 17 patients with ovarian metastases from CRC who underwent resection and 110 female CRC patients with Stage IV (M1a) disease. RESULTS: The patients with only ovarian metastases who underwent resection had a longer median survival time than patients with both ovarian and peritoneal metastases who underwent resection (45.4 months vs. 9.3 months, P = 0.029). The 5-year overall survival of the patients with only ovarian metastases who underwent R0 resection was as long as that of the female Stage IV (M1a) CRC patients after R0 resection (50% vs. 48%, P = 0.334). CONCLUSIONS: We found that, after resection, patients with only ovarian metastases had significantly better prognoses than patients with ovarian and peritoneal metastases. R0 resection of ovarian metastasis indicated as good prognosis as R0 resection of metastasis to one distant organ without ovaries. So the 9th edition of JCCRC, which classifies ovarian metastasis from CRC as distant metastasis, is appropriate.

[A Case of Locally Advanced Rectal Cancer with Multiple Liver Metastases Could Be Resected after Triplet Chemotherapy].

The patient was a 60's man, whose chief complaints were melena and weight loss. He visited our hospital, and further evaluation revealed rectal cancer(Ra)invading the abdominal wall with multiple liver metastases. The clinical diagnosis was cT4b(abdominal wall)N2bM1a(H1), cStage Ⅳ. We performed a transverse colostomy on the day prior to chemotherapy administration. He was administered 8 courses of FOLFOXIRI plus bevacizumab. After the chemotherapy, the primary tumor and liver metastases showed PR, with a diagnosis of ycT3N1bM1a(H1), Stage Ⅳ. We performed a robot-assisted laparoscopic low anterior resection for the primary tumor. Two months later, the partial resection of liver S6 and S8 was performed. The patient has been cancer-free for 6 months now.

[A Case of Giant Intestinal GIST That Was Resected Just after TAE].

A 42-year-old woman visited our hospital complaining of fever and diarrhea. She had abdominal swelling and muscular defense. CT revealed a lobulated tumor occupying the lower abdomen. The tumor contained solid and cystic areas. The main artery vascularizing the tumor was the ileocecal artery, so we considered the tumor to be derived from the intestine or mesentery. We anticipated massive bleeding due to resection, and immediately after the embolization of the artery just before the operation. A vascular bundle from the terminal ileum and mesentery was found on the dorsal side of the tumor, and an outflow from the inferior mesenteric vein was also observed. We ligated each vessel and performed ileocecal resection. The operation lasted 4 hours and 18 minutes, with an estimated blood loss of 2,585 mL, requiring the transfusion of 6 units of concentrated red blood cells. According to histopathological findings, tumor cells with spindle-shaped to ellipsoidal nuclei proliferated in bundles and intricately, and immunostaining was positive for c-kit and DOG-1. We identified the tumor as high-risk GIST. The clinical course after the operation was uneventful. She continued to take imatinib for 3 years and is currently alive and without recurrence for 6 years after the operation.

A case of multiple serous cystadenoma of pancreas.

INTRODUCTION: Typically, SCN is single and doesn't invade around tissue. In our case, tumors were multiple and had gradually grown and caused vein stenosis. This is extremely rare and unique resected multiple SCN case. In addition, I report that it was thought to be educational that even benign tumors could cause such changes. PRESENTATION OF CASE: A 60-year-old female was diagnosed with 3 multilocular cystic tumors in distal pancreas by contrast enhanced computed tomography (CT) at the preoperative staging for rectal neoplasm. The diameters of cystic tumors were 22/23/29 mm. The CT showed that the tumors had multiple internal septa enhanced in the arterial phase and the second tumor contained internal calcifications located centrally. The main pancreatic duct was not dilated. Although SCN often occurred single and multiple SCN was very rare, we diagnosed that the tumors were suspected microcystic type SCN because they had typical image findings. So, we planned to follow up every six months after resection for rectal neoplasm. 2 years and half later, they had gradually grown, and splenic vein stenosis appeared. The pancreatic parenchyma atrophy and dilatation of the main pancreatic duct had been gradually progressing. We performed distal pancreatectomy because of possibility of malignancy. The histopathological findings showed that 2 cystic tumors the side of pancreatic head had a connection and had typical findings of SCA of pancreas. The other tumor was independent from two tumors. They had no malignant findings. DISCUSSION: At first, we expected tumor invasion had caused the changes. But tumors had no malignant findings, so we considered that compression from the tumor had caused stenosis, and obstructive pancreatitis had induced the pancreatic parenchyma atrophy. CONCLUSION: We learned from this case that not only invasion but also compression caused vein stenosis and pancreatic duct dilation.

Surgical Outcome of Laparoscopic Cholecystectomy in Patients With a History of Gastrectomy.

BACKGROUND: Although laparoscopic cholecystectomy (LC) has been applied to patients with a history of abdominal surgery, we lack data on the surgical outcome of LC in patients with a history of gastrectomy. Here, we assessed the outcomes of LC and investigated predictive factors for conversion from laparoscopic to open surgery in patients with a gastrectomy history. PATIENTS AND METHODS: We retrospectively compared the surgical outcomes of LC between patients with and without a history of gastrectomy. We performed multivariate regressions to identify independent predictive factors for open conversion during an LC. RESULTS: Among 2235 patients who underwent LCs, 39 (1.7%) had undergone a previous gastrectomy (29 men, 10 women; mean age, 72 y; 34 with distal gastrectomy and 5 with total gastrectomy). The operation time, intraoperative bleeding, postoperative hospital stays, and conversion rate were significantly worse in patients with, compared with those without the history of gastrectomy. Conversion during an LC in the cases with a history of gastrectomy was significantly correlated with age and the type of gastrectomy. CONCLUSIONS: These results suggested that LC in patients with a history of gastrectomy exhibited worse outcomes in terms of operation time, intraoperative bleeding, postoperative hospital stay, and conversion rate than those without it. Furthermore, it was also implied that age and the type of gastrectomy were significant predictive factors for conversion during an LC in patients with a history of gastrectomy.

[A Resected Case of Hemorrhagic Hepatic Cyst Difficult to Differentiate from Mucinous Cystic Neoplasm of the Liver].

CASE: A 77-year-old woman was referred to our hospital for detailed examination of a cystic liver tumor. Contrast-enhanced CT and MRIshowed a cystic liver tumor with an enhanced mural nodule in S6 of the liver. Under a preoperative diagnosis of hemorrhagic hepatic cyst and mucinous cystic neoplasm(MCN)of the liver, extended posterior segmentectomy was performed. Histological examination of the tumor revealed no neoplastic cells, and the tumor was finally diagnosed as a hemorrhagic hepatic cyst of the liver. CONCLUSION: Similar to previous reports of hemorrhagic hepatic cysts, preoperative differential diagnosis from MCN of the liver was difficult in this case. Hemorrhagic hepatic cysts are rare and are sometimes confused with MCN of the liver, especially when an enhanced mural nodule is found in the cyst. The possibility of hemorrhagic hepatic cysts should be considered during diagnosis of liver cystic tumors.

[Long-Term Survival in a Case of Colon Cancer with Peritoneal Dissemination and Ovarian Metastasis after Multimodality Therapy].

A 70-year-old woman underwent treatment for cecal cancer(pT4bN1M0, Stage Ⅲb)in 2010. Four years and 2 months after the first surgery, she underwent ileum resection for stenosis due to perineal dissemination(P3). Two years after this recurrence, during which time she had completed 26 courses of FOLFIRI plus bevacizumab(Bmab), 9 courses of capecitabine plus oxaliplatin(CapeOX)plus Bmab, and 3 courses of Cape, no peritoneal dissemination was detected by computed tomography( CT). Thereafter, an additional 19 courses of Cape plus Bmab were introduced, but CEA continued to increase. Right ovarian metastasis was suspected based on CT and FDG-PET/CT examination. Four years and 1 month after the initial recurrence of perineal dissemination, the patient underwent bilateral ovarian resection, during which the lack of peritoneal dissemination was confirmed. Pathologically, right ovarian metastasis was diagnosed. The patient is still alive 4 years and 6 months after the first operation.

[Gastric Gastrointestinal Stromal Tumor Appearing Nine Years after Resection of a Duodenal Gastrointestinal Stromal Tumor-A Case Report].

Multiple sporadic gastrointestinal stromal tumor(GIST)are rare, except for those restricted to von Recklinghausen disease or hereditary conditions.We reported a case of a gastric GIST resected 9 years after the resection of a duodenal GIST.The patient was a 58-year-old male who had been followed-up with computed tomography scans after pancreatoduodenectomy for a duodenal GIST when he was 49-years-old.The patient was admitted to our hospital for anemia examination.A CT scan detected a tumor in the stomach, with a diameter of over 10 cm, and necrosis.Esophagogastroduodenoscopy revealed the presence of a delle on the gastric SMT.Due to suspected invasion of the spleen and left diaphragm by the tumor, we performed subtotal gastrectomy with splenectomy and left diaphragm segmental resection.In the pathological diagnosis, the tumor was diagnosed as a gastric GIST, because the cell type of the tumor was spindle and tested positive for c-kit.Based on the tumor size and mitotic count, the patient was diagnosed with high-risk GIST by the modified-Fletcher classification, and imatinib 400mg/day was administered.There have been no signs of recurrence for 2 years since the operation.