[Preoperative Prognostic Factors in CRS plus HIPEC for Patients with Peritoneal Dissemination of Colorectal Cancer].

Peritoneal dissemination of colorectal cancer has the poorest prognosis among metastatic sites, with an average overall survival of less than 6 months. Various treatment methods have been reported for these patients, and recently there have been several reports showing the usefulness of cytoreductive surgery(CRS)combined with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the studies on this treatment are limited. In this study, we retrospectively reviewed cases of CRS plus HIPEC. Twenty-one patients who underwent CRS plus HIPEC at Tokyo Medical University Hospital and Toda Central General Hospital between August 2014 and December 2017 were included in this study. The long-term and short-term survival groups were analyzed separately, and predictors of preoperative treatment efficacy were examined. The surgical approach was open in 16 cases and laparoscopic in 5 cases. Complete resection was achieved in 10 of these patients. Postoperative complications occurred in 6 patients. There were no deaths within 90 days of surgery. The median overall survival was 17.0 months, and the 1-year survival rate was 65%. Median progression-free survival was 11.0 months. In a multivariate analysis predicting long-term versus short-term survival groups, sex, primary tumor location, and P factor were independent predictors of treatment response. CRS plus HIPEC therapy is considered an effective treatment option. The predictors of preoperative treatment response include sex, primary tumor location, and P factor.

Prospective Multicenter Phase II Study of Biweekly TAS-102 and Bevacizumab for Metastatic Colorectal Cancer.

BACKGROUND: This study assessed the efficacy and safety of biweekly trifluridine and tipiracil hydrochloride (TAS-102) with bevacizumab combination therapy for patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: We included 19 patients with mCRC who received TAS-102 and bevacizumab combination therapy biweekly as third-line chemotherapy. The primary endpoint was progression-free survival. RESULTS: Patients had a median age of 73 years and most (73.4%) were men. The median progression-free and overall survival were 5.6 and 11.5 months, respectively. Five (26.3%) patients achieved a response and the disease control rate was 12/19 (63.1%). One patient (5.2%) experienced neutropenia grade 3 or more. The median time from baseline performance status 0/1 to worsening to 2 or more was 10.3 months. CONCLUSION: Biweekly TAS-102 plus bevacizumab facilitates tumor shrinkage by reducing the incidence of grade 3 or more neutropenia, improving survival, and maintaining performance status. This combination may represent a treatment option for patients with late-stage mCRC receiving third- or later-line therapy.

[A Case of Diffuse Large B-Cell Lymphoma of the Testis, Which Also Developed in the Rectum after Resection of a Large B-Cell Lymphoma].

A man aged 65 years had undergone high orchidectomy of the right testis for diffuse large B-cell lymphoma(DLBCL) occurring primarily in the testis 11 months before. Although he was referred to another hospital for postoperative chemotherapy, he refused the treatment by self-judgement. For 1 month, he had been experiencing melena and anal pain, so he visited our department in June. Rectal palpation revealed a sub-circumference tumor palpable from the anal margin, in which a part protruded outside the anus. CT revealed a sub-circumference hypertrophic wall from the rectal Ra to the anus and intramural enlarged lymph nodes, without metastases to the other organs. Systemic gallium scintigraphy detected a strong concentration in the rectum. The endoscopic examination of the inferior region revealed a circumference type 2 tumor at Rb, and biopsy revealed DLBCL. Clinically, this case was considered a testoid DLBCL with rectal metastasis. Therefore, we performed laparoscopic rectal amputation in July, XX. sT3N1b, cM0. The postoperative course was uneventful. After the patient was discharged from our department, he received chemotherapy at another hospital. At present, 4 years 0 month postoperatively, the patient condition is favorable without recurrence. When perforation occurs in gastrointestinal DLBCL, the start of chemotherapy is delayed and the primary lesion worsen. Therefore, we performed surgical therapy first. Such cases must be evaluated for metastases or new lesions carefully.

[A Case of Isolated Metachronous Splenic Metastasis after Rectal Cancer Surgery].

A 50-year-old woman underwent laparotomic anterior resection(D3)and total hysterectomy with bilateral adnexectomy (type 2, 3.0×4.5 cm, pT4a[SE], N1a, M1c2[ovary and peritoneum], H0, P1, PUL0, stage Ⅳc, tub2>por, Cur B)for ovarian metastasis from rectal cancer in June 20XX. During the outpatient visit in May, 2 years and 11 months after surgery, a splenic tumor was found on abdominal contrast-enhanced CT, without distant metastasis in other organs. In July 20XX, laparoscopic splenectomy was performed for suspected splenic metastasis of rectal cancer. The specimen of the resected tumor showed pathological findings consistent with metastasis of rectal cancer. Currently, the patient is being followed up without any sign of recurrence. Herein, we report a rare case of isolated metachronous splenic metastasis, whose associated prognosis might be improved by surgical treatment, in reference to the literature.

[A Case of Sigmoid Colon Neuroendocrine Cell Carcinoma Discovered by Defecation Disorder].

A 65-year-old man presented to our hospital with a chief complaint of abdominal pain during defecation. Abdominal contrast-enhanced CT showed circumferential wall thickening with contrast effects in the sigmoid colon, and multiple metastases in the liver. Colonoscopy revealed a type 2 colon tumor that was obstructing the passage. A diagnosis of sigmoid colon cancer and multiple liver metastases was made based on laparoscopic sigmoidectomy plus D3 dissection. Pathologically, the resected specimen was diagnosed as colorectal neuroendocrine cell carcinoma(NEC)that was positive for synaptophysin and CD56. Postoperatively, 8 courses of FOLFOX plus bevacizumab(BV)therapy were administered, but CT showed remarkable increase in liver metastasis, and he died 5 months after the operation. Colorectal NEC is a very rare disease, for which no chemotherapy has been shown to be effective. Since we encounterd a case of sigmoid colon NEC with multiple liver metastases that followed a rapid course, we have presented it along with a literature review.

[Efficacy of 89Sr as Pain Relief for Gastric Cancer Bone Metastasis].

We experienced 2 cases in which strontium chloride was used for pain associated with gastric cancer bone metastasis. Case 1 was of a 69-year-old woman. In 2015, she underwent surgery for advanced gastric cancer followed by adjuvant chemotherapy with S-1 for 1 year. Multiple bone metastases were confirmed 2 years and 3 months after surgery. Obvious pain relief was obtained after 89Sr was administered, and SOX therapy was started. Case 2 was of a 62-year-old man. In 2016, he underwent curative surgery for stomach cancer. Chemotherapy with S-1 was performed for approximately 6 months, but 9 months after surgery multiple LN metastases, liver metastasis, and multiple bone metastases were observed . In case 2, 89Sr was administered, but good pain control was not obtained. The use of 89Sr for pain relief against multiple bone metastases should be based on the previous literature.

GSTP1 as a potential predictive factor for adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy.

Glutathione S-transferase (GST) exhibits antidotal effects on numerous drugs, including platinum-based antineoplastic drugs. Furthermore, GST Pi 1 (GSTP1) polymorphism is associated with peripheral neuropathy. In the present study, it was determined whether GSTP1 can predict adverse events associated with platinum-based antitumor agent-induced peripheral neuropathy among Japanese patients. The subjects included 122 patients, among whom 105 patients had colorectal, 16 had gastric, and one patient had pancreatic cancer. It was indicated that wild type (AA) GSTP1 was expressed in 99 patients (81.1%), whereas heterozygous (AG) and homozygous (GG) GSTP1 polymorphisms were present in 22 (18.0%) and 1 (0.8%) patients, respectively. Among patients with colorectal cancer, the expression of homozygous GSTP1 was observed in 88 patients (83.8%), whereas that of heterozygous GSTP1 was observed in 17 patients (16.2%). Peripheral neuropathy of grade ≥3 occurred in 10 patients (9.5%) receiving mFOLFOX therapy (a biweekly cycle consisting of a 2-h infusion of 85 mg/m2 oxaliplatin and 200 mg/m2 leucovorin followed by a bolus administration of 400 mg/m2 5-fluorouracil and a continuous 48-h infusion of 2,400 mg/m2 5-fluorouracil) for colorectal cancer, which included 6 patients with the AA allele (6.8%) and 4 patients with the AG allele (23.5%). The number of peripheral neuropathy cases of grade ≥3 was increased among patients with the AG allele, compared with patients with the AA allele (P=0.032). In patients with gastric cancer, the AA and AG types of GSTP1 were expressed in 11 (68.8%) and 5 (31.2%) patients, respectively. Cisplatin, administered to patients with gastric cancer, did not induce peripheral neuropathy. The aforementioned indicated that GSTP1 genetic polymorphism is associated with peripheral neuropathy induced by oxaliplatin treatment for colorectal cancer, and therefore serves as a predictive marker. Furthermore, early dose reduction or drug withdrawal should be implemented depending on the severity of peripheral neuropathy as a potential method for reducing the number of patients discontinuing the drug, due to adverse events involving peripheral neuropathy.

[A Case of Diverticular Perforation of Sigmoid Colostomy during FOLFIRI plus BevacizumabTreatment].

A 61-year-old man with a diagnosis of rectal cancer underwent assisted laparoscopic rectal amputation. Recurrence occurred, and treatment with FOLFIRI plus bevacizumab was initiated at our department. After 12 treatment courses, he developed abdominal pain at home. Emergency surgery was performed for the stoma perforation. We confirmed the diverticular perforation in the resected specimen. In our case, we found a para-stoma hernia and considered it to be the cause of perforation together with bevacizumab administration. Molecular-targeted drugs contribute to improving treatment outcomes in malignant tumors, but specific adverse events such as perforation have been reported. In addition, as causes of sigmoid colon perforation such as that of the stoma, cases associated with intestinal operation, constipation, and para-stoma hernia are suggested. In our case of hyperpolarization due to a para-stoma hernia, administration of bevacizumab was considered the cause of the perforation. This was a case that could be rescued with surgery.

Why Does Postoperative Pancreatic Fistula Occur After Hand-sewn Parenchymal Closure and Staple Closure in Distal Pancreatectomy?

Hand-sewing (HS) and stapling are common parenchymal closure techniques after distal pancreatectomy. However, these methods cannot completely prevent postoperative pancreatic fistula (POPF). The mechanisms of POPF formation after closure are unknown. We performed distal pancreatectomy in mongrel dogs to identify the mechanisms of POPF formation after HS and staple closure. We measured the closed pancreatic duct burst pressures and examined the histology of the remnant pancreas. The after staple-closure burst pressures depended on stapler height; lower pressures were associated with greater stapler heights. Post-HS closure burst pressures were significantly higher than those at each stapler height (P<0.01). Post-HS closure pathologic findings showed extensive necrosis (day 3), and some regenerated pancreatic duct stumps (day 5). Necrosis was not observed around the stapled tissues. Although HS completely closes the pancreatic ducts, stump necrosis and blood flow disturbances may cause POPF. With stapler closure, pancreatic fluid leakage may occur even with appropriate stapler heights.

[Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with Transanal Minimally Invasive Surgery].

A46 -year-old man developed ulcerative colitis at the age of 19 years. Although the colitis was medically treated, it relapsed and repeated over time. Periodic lower gastrointestinal endoscopy revealed lower rectal cancer, and he was referred to our department of surgery. Previous steroid therapy induced diabetes, and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89 kg/m2, indicating that laparoscopic dissection near the anus would be difficult to perform. Therefore, the patient was scheduled for transanal minimally invasive surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as possible in the ventral to dorsal direction, followed by the TAMIS procedure. Dissection was started from the dentate line, and, after the closure of the anal stump, GelPOINT was placed, and made continuous with the previous dissection layer by applying the technique of down-to-up total mesorectal excision(TME)by TAMIS. The large intestine was excised through a small abdominal incision to create an ileal pouch, hand-sewn anastomosis was performed transanally to create a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several problems remain to be solved, including an understanding of its unique anatomy and the mastery of single-port surgical techniques. However, the herein reported patient with a high BMI had a definite indication for TAMIS-TME.

[A Long-Term Disease-Free Survival Case of Synchronous Pulmonary and Liver Metastasis of Rectal Cancer with Systemic Chemotherapy and Radiofrequency Ablation Therapy for Liver Metastasis].

A 55-year-old woman underwent laparoscopic anterior resection and D2 lymph node dissection for recto-sigmoid colon cancer in November 2014, which was diagnosed as T3N1M1(H3, PUL2), stage IV , for the purpose of preserving the ileus. FOLFOX therapy with panitumumab(Pmab)was started in January 2015.A t the end of 11 courses, pulmonary metastasis changed to CR, and liver metastasis was down-graded to H2 on the CT.Because of the risk of hepatic dysfunction with advanced fatty liver due to chemotherapy and extrahepatic lesions, we chose radiofrequency ablation(RFA)therapy for liver metastasis.Pmab combined FOLFIRI therapy was administered, and maintenance therapy was initiated.This patient is alive 2 years and 7 months after surgery and 10 months after RFA without relapse.It is suggested that RFA therapy for liver metastasis of colon cancer with pulmonary metastasis combined with chemotherapy could be an effective treatment strategy.

[Two Cases of Non-Occlusive Mesenteric Ischemia That Developed after Chemotherapy].

Non-occlusive mesenteric ischemia(NOMI)causes intestinal necrosis due to irreversible ischemia of the intestinal tract despite the absence of organic obstruction in the mesenteric blood vessels. The disease has extremely poor prognosis. We encountered 2 cases of NOMI hypothesized to have developed after chemotherapy; thus, we report these cases considering the available literature. Case 1: A7 9-year-old man. The patient complained of abdominal pain during the first week after introducing docetaxel for local recurrence of prostate cancer. Abdominal computed tomography(CT)revealed mesenteric ischemia and intestinal emphysema. The patient was diagnosed with NOMI, and an emergency operation was performed. Upon laparotomy, the small intestine; ascending, transverse, and descending colon; recto sigmoid; and gall bladder appeared mottled necrotic. As such, all these were excised. He was admitted back to the hospital 3 weeks after surgery due to pneumonia. Case 2: A7 4-year-old man. Combination chemotherapy of docetaxel, cisplatin, and 5-FU was given for oropharyngeal cancer. After 1 week, fever and abdominal pain were noted. Abdominal contrast CT examination was performed, and mesenteric ischemia was confirmed as NOMI. Emergency surgery was performed on the same day. The entire ileum was discolored with mottling, and it was determined to be necrotic. Thus, it was excised. Postoperative course is good, and the patient was followed up after discharge from the hospital. Before NOMI onset in both cases, docetaxel was used to treat myelosuppression. Considering the patient conditions, the association between NOMI onset and docetaxel was suspected. In general, mesenteric ischemia after administration of anticancer drugs is rare, and only a few cases have been reported.

[A Case Where Function Preservation Was Possible for Quadruple Cancer Metastasis].

The patient was a 69-year-old man visited our hospital because of fecal occlt blood test at medical checkup and diagnosed with rectal cancer and gastric cancer. The patient underwent super low anterior resection for rectal cancer cStage III b and underwent endoscopic submucosal dissection(ESD)for early gastric cancer. In 1 year after surgery the patient had recurrence of gastric cancer after ESD and recurrent gastric cancer was additionally resected. In 1 year and 4 months after surgery pulmonary metastasis was recognized and the patient underwent pulmonary segmentectomy. In 5 years after surgery renal cell carcinoma was recognized and the patient underwent partical renal excision. In 8 years after surgery esophagus cancer was recognized and the patient underwent radical chemoradiationtherapy and completed local complete remission. Current the patient is alive without relapse. We report a case where function preservation was possible for quadruple cancer by appropriate preoperative and postoperative examination and appropriate treatment.

[Treatment Outcome of Intersphincteric Resection in Tokyo Medical University Hospital].

PURPOSE: This study aimed to consider the oncological validity of intersphincteric resection(hereinafter referred to as ISR) performed at Tokyo Medical University Hospital, as well as associated dysfunction. SUBJECTS: Subjects included 73 cases in which ISR was performed at Tokyo Medical University Hospital between November 2004 and January 2016. RESULTS: The 5- year overall and relapse-free survival rates for cases with Stage 0 to III were 90.4% and 77.3%, respectively. Two cases with recurrence among cases with Stage I were both of local recurrence.The Wexner score of the cases 12 months after closure of ileostomy was 4.2±2.5 points, while it had not been performed for the other 10 cases. DISCUSSION: In consideration of the relatively preferable local control observed with ISRs that had been performed at our hospital, defecation disorder was considered to be within an allowance.However, there remained a problem that closure of ileostomy could not be performed for 10% of the cases. CONCLUSION: ISR was believed to be valid as a sphincter-preserving procedure in consideration of the function and curability.

Successful laparoscopic resection of a retroperitoneal schwannoma arising from the femoral nerve: A case report.

We report on a 45-year-old man who presented with pain in the left leg, which he had had for 2 months. A contrast-enhanced CT scan displayed a 25-mm tumor in the lateral side of the left psoas muscle. For this suspected retroperitoneal tumor, we performed laparoscopic resection of the tumor, which was encapsulated by the funicular femoral nerve, using surgical scissors rather than a surgical energy device and preserved the normal fascicles wherever possible. Pathological examination indicated a benign ancient schwannoma arising from the femoral nerve. The patient was able to return to his job 3 weeks after surgery, and he has shown no evidence of recurrence. This was thought to be because of the use of surgical scissors, rather than a surgical energy device, combined with visual magnification. Therefore, the laparoscopic approach is an effective and minimally invasive option for the resection of femoral nerve schwannoma.

[Radiofrequency Ablation Combined with Hepatectomy for the Treatment of Liver Metastases from Colorectal Cancer].

OBJECTIVE: We evaluated hepatectomy combined with radiofrequency ablation(RFA)in patients with liver metastases from colorectal cancer for which curative resection is difficult. METHODS: This study included 13 patients who underwent hepatectomy combined with RFA for liver metastases from colorectal cancer in or before 2015. RESULTS: In 11 patients who were determined to have achieved a complete curative resection, the 50%survival time was 35.4 months, and the 5-year overall survival (OS)rate was 33%. Recurrence at the RFA site was observed in 4 patients. There were 2 patients with a long-term survival of 5-years or longer. The reasons for concomitant use of RFA include deviation from the Makuuchi criteria in 4 patients, control of disease progression in 3 patients, non-curative surgery in 2 patients, difficulty in performing surgical procedures in 2 patients, and refusal by 1 patient, while the reason was unknown in 1 patient. DISCUSSION: Hepatectomy combined with RFA was selected in patients in whom curative hepatectomy was impossible. Although their 5-year OS rate was lower than that of patients who undergo hepatectomy alone, local control was relatively favorable. CONCLUSION: These results suggest that hepatectomy combined with RFA for liver metastases from colorectal cancer might be effective in selected cases.

[Examination to Determine Predictive Factors of Effectiveness of Surgical Treatment for Both Pulmonary and Hepatic Metastasis from Colorectal Cancer].

In recent years, several colorectal patients with pulmonary and hepatic metastasis, if resectable, have been found to experience long-term survival. In the present study, we extracted predictive factors, selected patients for whom a good prognosis could be anticipated, and examined the indications for surgery. From January 1986 to December 2014, we conducted a multivariate analysis of 18 patients who underwent surgical resection for pulmonary and hepatic metastases, with overall survival(OS)as the dependent variable, and clinicopathological factors as explanatory variables. The 5-year survival rate of the pulmonary and hepatic resection group was 32.0%. No significant difference was noted observed in CEA levels, number of metastatic pulmonary nodes, tumor diameter, synchronic, and metachronous tumors. A significant difference was only observed for disease-free interval(DFI)following resection of the primary lesion. The area under the receiver operating characteristic(ROC)curve revealed that the optimum cut-off value following resection of the primary lesion was a DFI of 762 days. When comparing the OS of the group with DFI<762 days and the group with DFI<762 days using a Kaplan-Meier curve, we found that survival was significantly prolonged. Therefore, surgery is indicated for colorectal cancer patients with pulmonary and hepatic metastasis, and who have DFI>2 years following resection of the primary lesion, and prolonged survival can be expected following surgery.

[A Case of Advanced Rectal Cancer in Which Combined Prostate Removal and ISR Using the da Vinci Surgical System with Preoperative Chemotherapy Allowed Curative Resection].

A 53-year-old male presented with a chief complaint of dyschezia.Lower gastrointestinal endoscopy confirmed the presence of a type II tumor in the lower part of the rectum, and a biopsy detected a well-differentiated adenocarcinoma.As invasion of the prostate and levator muscle of the anus was suspected on diagnostic imaging, surgery was performed after preoperative chemotherapy.With no clear postoperative complications, the patient was discharged 26 days after surgery. After 24 months, the number of urination ranged from 1 to 6, with a Wexner score of 6 and a mild desire to urinate in the absence of incontinence.At present, the patient is alive without recurrence.When combined with chemotherapy, robotassisted surgery allows the curative resection of extensive rectal cancer involving the suspected invasion of other organs.In this respect, it is likely to be a useful method to conserve anal and bladder function.

[Four Patients Who Underwent Lateral Lymph Node Dissection by an Extraperitoneal Approach for Lateral Lymph Node Recurrence FollowingSurg ery for Rectal Cancer].

To date, the surgical approach for recurrent rectal cancer has often involved highly invasive procedures. We report our experience of 4 patients who underwent lateral lymph node dissection via an extraperitoneal approach for lateral lymph node recurrence following surgery for rectal cancer. Patient 1 was a 60-year-old woman who, 6 months after surgery, underwent surgery for lateral lymph node recurrence in 1 node. Patient 2 was a 71-year-old man who underwent surgery after colostomy for rectal cancer and 4 courses of FOLFIRI+panitumumab resulted in a PR. Five months later, he underwent left lateral lymph node dissection. Patient 3 was a 78-year-old man who underwent postoperative adjuvant chemotherapy. Ten months later he underwent colostomy closure+left lateral lymph node dissection. Patient 4 was a 66-year-old man who underwent colostomy closure+lateral lymph node dissection with concurrent resection of the right internal artery. In 3 out of 4 patients, meal intake was recommenced on day 4 after surgery, and the patients were discharged without any complications. Furthermore, 3 out of the 4 patients were recurrence-free at 19 months. We believe that our results with regards to complications and duration until meal recommencement were better than those for conventional surgery for lymph node recurrence.

Complete laparoscopic resection of the rectum using natural orifice specimen extraction.

AIM: To investigate how complete laparoscopic anterior resection with natural orifice specimen extraction (NOSE), as a novel minimally invasive surgery, compares to conventional laparoscopic surgery. METHODS: Twenty patients who underwent complete laparoscopic anterior resection with NOSE and 50 patients who underwent laparoscopic assisted anterior resection by the conventional method between 2011 and 2012 were studied. Selection for complete laparoscopic anterior resection with NOSE was decided on the basis of tumor size, localization of the tumor, and body mass index. Outcomes related to surgery, including operation time, postoperative wound pain, hospital stay after surgery, the number of totally dissected lymph nodes, postoperative complications (suture failure and wound infection), and anal function, were reviewed retrospectively. Anal function was assessed at 3 and 6 mo after surgery using the Wexner fecal incontinence scoring system. RESULTS: Complete laparoscopic resection with NOSE was performed to completion in all 20 patients. There was no patient emergency that required conversion to conventional laparoscopic surgery or open surgery. The comparison between complete laparoscopic resection with NOSE and conventional laparoscopic surgery showed no significant differences in the maximal diameter of the tumor, number of totally dissected lymph nodes, bleeding volume, mean operation time, time to start of oral ingestion, postoperative hospital stay, and postoperative complications. On the other hand, with regard to pain after epidural anesthesia, the total usage of analgesia in this novel surgical technique was 1.85 ± 1.8 times, whereas it was 5.89 ± 2.86 in conventional laparoscopic surgery (P < 0.001). The postoperative pain period was 1.9 ± 1.9 d in this novel surgical technique, whereas it was 3.43 ± 1.41 d in conventional laparoscopic surgery (P < 0.004). In complete laparoscopic surgery with NOSE, the mean postoperative follow-up period was 20 mo (range: 12-30 mo). Neither local recurrence nor remote metastasis was observed during the follow-up period. CONCLUSION: Complete laparoscopic anterior resection using NOSE does not require any incision and has excellent cosmetic properties, with mitigated postoperative pain.