High hand grip strength is a significant risk factor and a useful predictor of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most critical complications of pancreaticoduodenectomy (PD). Studies on predictive factors for POPF that can be identified preoperatively are limited. Recent reports have highlighted the association between the preoperative nutritional status, including sarcopenia, and postoperative complications. We examined preoperative risk factors for POPF after PD, focusing on nutritional indicators. METHODS: A total of 153 consecutive patients who underwent PD at our institution were enrolled in this study. Preoperative nutritional parameters, including hand grip strength (HGS) and skeletal muscle mass as components of sarcopenia, were incorporated into the analysis. POPFs were categorized according to the International Study Group of Pancreatic Fistula (ISGPF) definition as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). RESULTS: Thirty-seven of the 153 patients (24.1%) fulfilled the ISGPF definition of CR-POPF postoperatively. In the univariate analysis, the incidence of CR-POPF was associated with male sex, non-pancreatic tumor diseases, a high body mass index, a high HGS and a high skeletal muscle mass index. In the multivariate analysis, non-pancreatic tumor diseases and an HGS ≥23.0 kg were selected as independent risk factors for CR-POPF (P <0.05). CONCLUSIONS: A high HGS, a screening tool for sarcopenia, was a risk factor for CR-POPF. It can accurately serve as a useful predictor of POPF risk in patients undergoing PD. These results highlight the potential of sarcopenia to reduce the incidence of POPF and highlight the need to clarify the mechanism of POPF occurrence.

Erratum forTotal Neoadjuvant Chemotherapy in Rectal Cancer: Current Facts and Future Strategies.

[This corrects the article DOI: 10.23922/jarc.2022-060.].

Total Neoadjuvant Chemotherapy in Rectal Cancer: Current Facts and Future Strategies.

Despite preoperative chemoradiotherapy (CRT) and total mesorectal excision improving the local control for locally advanced rectal cancer (LARC), oncologic outcomes and survival were not significantly improved because the main prognostic factor is distant metastasis. Thus, total neoadjuvant chemotherapy (TNT) as a novel approach has been proposed to improve chemotolerance. Since the first randomized phase II trial of TNT versus standard CRT demonstrated in 2012, many prospective and retrospective studies have been published. The initial consensus from TNT studies was that pathological complete response, pathological response of the main tumor, and local control are more favorable at TNT than at CRT. Furthermore, recent studies such as the PAPIDO trial and PRODIGE 23 trial made a major breakthrough of the treatment of TNT, showing that TNT improves the disease-free survival compared to standard treatment with long-course CRT. In addition, several innovative findings of TNT were clarified by prospective phase II trial. In this review, we summarize the most recent advances in TNT based on the findings of pivotal clinical trials for patients with LARC.

[Two Cases of Elderly Patients with Giant Intrahepatic Cholangiocarcinoma Treated with Multidisciplinary Therapy including Ablation Therapy].

Case 1 consisted of an 86-year-old male diagnosed with intrahepatic cholangiocarcinoma(ICC), approximately 11 cm in diameter, at segment S7/8 of the liver. A total of 4 percutaneous radiofrequency ablations(PRFA)and 3 hepatic arterial infusion chemotherapies(HAIC)of 5-FU were performed. He died after developing lung metastases 27 months after the initial treatment. Case 2 was an 85-year-old female diagnosed with ICC, 8 cm in diameter, at the posterior segment of the liver, with lymph node metastasis. She underwent HAIC of 5-FU and S-1 as well as gemcitabine-based systemic chemotherapy. The main tumor developed 10 months after the initial treatment, and PRFAs were subsequently performed twice for the main lesion. Although the tumor markers gradually decreased, she died of jaundice 33 months after the initial treatment. As one of the multidisciplinary therapies for the giant ICC, ablation therapy may be safe and effective in elderly patients.

[Clinical Study of Peritoneovenous Shunt for Patients with Refractory Ascites Accompanied with Hepatocellular Carcinoma].

BACKGROUND: Hepatic ascites may cause a variety of symptoms and may progress deterioration of quality of life. Peritoneovenous shunt(PV shunt)is technically feasible and useful for the treating of refractory ascites, but sometimes it can be associated with fatal complications. This retrospective study aimed to investigate the effect of PV shunt for patients with refractory ascites, including hepatocellular carcinoma(HCC)patients. SUBJECTS: Between January 2010 and December 2021, we retrospectively analyzed 54 consecutive patients(including 35 HCC patients)with refractory ascites who underwent PV shunt at our institute. RESULTS: Body weight loss after surgery was observed in 39 of the 54 cases, and eGFR improved in 34 cases. There were 17(31.5%)in-hospital deaths. Cases with present of portal vein tumor thrombus, Child-Pugh classification C, ALBI score≥-1.12, or serum total bilirubin≥1.7 mg/dL were significantly higher in hospital-death group than in the discharged from the hospital group. CONCLUSIONS: PV shunt for HCC patients with refractory ascites may be effective for improvement of renal function and symptoms. However, indications for PV shunt should be carefully considered for high-risk patients with adequate preoperative evaluation.

[A Case of Long-Term Survival with S-1/Cisplatin for Liver Hilum Lymph Node Metastasis of Anal Canal Squamous Cell Carcinoma after Chemoradiotherapy].

A 70-year-old woman was admitted to a local hospital because of anal pain during defecation. Anoscopy revealed an anal mass lesion, and the patient was referred to our hospital. Colonoscopy revealed an anal canal tumor with ulceration, and biopsy showed squamous cell carcinoma. The patient was treated with chemoradiotherapy(chemotherapy with capecitabine plus mitomycin C and 54 Gy radiation in the anal region)and achieved complete response. However, metastatic recurrence was detected in a lymph node in the hepatic hilar region. We administered an S-1/CDDP combination chemotherapy (5 courses). For 3 years and 5 months since the initial treatment, the patient survived with no signs of recurrence. We report a rare case of long-term survival with S-1/CDDP for distant metastasis of anal canal squamous cell carcinoma after chemoradiotherapy.

[Clinical Efficacy of Recombinant Human Thrombomodulin for Surgical Patients with Disseminated Intravascular Coagulation Associated with Oncologic Emergency].

AIM: We evaluated the clinical efficacy of recombinant human thrombomodulin(rTM)for surgical patients with disseminated intravascular coagulation syndrome(DIC)associated with an oncologic emergency(OE). SUBJECTS AND METHODS: Thirteen patients who underwent surgery for OE complicated with DIC and were treated with rTM in our institution were evaluated. We retrospectively analyzed the clinical changes of parameters in white blood cell count(WBC), platelet count, CRP, PT-INR and DIC scores after the rTM treatment. RESULTS: The average length of the days using rTM was 4.7 for 12 patients, excluding one who died within 30 days after surgery. Nine of 12 patients(75%)had DIC scores of less than 3 after the rTM treatment. WBC tended to decrease after the rTM treatment, without statistical difference. However, CRP, platelet count, PT-INR and DIC scores were significantly improved after the rTM treatment(p<0.05). CONCLUSIONS: rTM may be useful in the treatment of DIC for surgical OE patients.

[A Rapid Clinical Course of Pulmonary Embolism Associated with Gallbladder Mucinous Carcinoma].

A 51-year-old woman with edema of the lower extremities and exertional dyspnea was admitted to our hospital. Enhanced CT revealed thrombi of the pulmonary artery and a gallbladder tumor. After anticoagulation therapy was started on her, anemia and jaundice progressed; thus, endoscopic retrograde cholangiopancreatography(ERCP)was performed on suspicion of bleeding from a gallbladder tumor. We performed cholecystectomy in emergency to control the anemia due to hemorrhage. Oxygenation suddenly worsened intraoperatively, maintaining her blood pressure became difficult, and the patient decompensated. The histopathological diagnosis was gallbladder mucinous carcinoma with severe lymphatic invasion. Although an autopsy was not performed, pulmonary artery embolism derived from a tumor embolus was the suspected cause of the sudden change of the clinical course.

Phase II study of S-1-based sequential combination chemotherapy including oxaliplatin plus bevacizumab and irinotecan with or without cetuximab for metastatic colorectal cancer: the SOBIC trial.

BACKGROUND: Fluorouracil and leucovorin combined with oxaliplatin or irinotecan plus bevacizumab (Bmab) or cetuximab (Cmab) are now widely accepted treatment options as first-line or second-line chemotherapy for metastatic colorectal cancer (mCRC). Sequential chemotherapy with oral 5-FU backbone for mCRC without using central venous ports is beneficial for both patients and physicians. We designed the SOBIC trial to validate the effectiveness of the first- and second-line oral combination chemotherapy for mCRC. PATIENTS AND METHODS: From May 2010 through March 2013, 52 patients were enrolled from 47 institutions in the Hyogo Colorectal Cancer Surgery Group. First-line chemotherapy was S-1 + oxaliplatin (SOX) plus Bmab, and second-line chemotherapy after first-line failure was irinotecan + S-1 (IRIS) + Cmab, IRIS + Bmab, or IRIS based on the KRAS status. RESULTS: The 50 finally included patients received first-line chemotherapy. Second-line therapy was administered to 20 patients (40%): 12 patients received IRIS + Cmab and 8 patients received IRIS + Bmab. The median follow-up period was 48.6 months (range 35-67 months). The median second progression-free survival was 24.2 months (95% confidence interval [CI] 17.7-35.2). The response rate after first- and second-line chemotherapy was 46.7% and 15%, respectively. The median overall survival was 35.2 months (95% CI: 27.8 to not reached). The main grade 3-4 adverse events were sensory neuropathy (18%) and fatigue (10%). There were no treatment-related deaths. CONCLUSION: Sequential S-1-based combination regimens including oxaliplatin, irinotecan, Bmab, and Cmab were beneficial for patients with mCRC.

S-1, Oxaliplatin, Nab-paclitaxel and Itraconazole for Conversion Surgery for Advanced or Recurrent Gastric Cancer.

AIM: To evaluate the efficacy of chemotherapy with itraconazole for advanced or recurrent gastric cancer. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2 (HER2) negative unresectable gastric cancer referred to our hospital were included. The regimen comprised 160 mg/m2 nab-paclitaxel i.v. and 100 mg/m2 oxaliplatin i.v. on day 1, 60 mg/m2 S-1 orally on days 1-3, and 400 mg itraconazole orally on days -2 to 2, repeated every 2 weeks for 6-8 cycles. RESULTS: Twenty-three patients aged 40-80 years (median age=68 years) were enrolled, of whom 21 had stomach cancer and two gastroesophageal junction cancer. Regarding stage, two, one, and 20 patients had stage IIIA, IIIB, and IV, respectively. Among patients with liver metastases, 2/10 had simultaneous lung metastases. Nine patients had peritoneal dissemination, and five patients with stage IV disease developed recurrence after primary surgery followed by adjuvant S-1. The other 18 patients had no history of surgery or chemotherapy. The response rate was 70% (complete response in two; partial response in 14). Among 12 patients (67%) who underwent conversion surgery, R0 resection was conducted in eight, and no residual tumour was observed in two. For the population overall, the median overall survival was 24 months (95% confidence intervaI=21 months-not reached) and the 1-year overall survival rate was 95% (95% confidence intervaI=67-98%). Grade 3/4 neutropenia and grade 2 peripheral sensory neuropathy occurred in five (22%) and six (26%) patients, respectively, while no patient developed grade 3/4 thrombocytopenia. CONCLUSION: Chemotherapy with itraconazole is promising for patients with unresectable gastric cancer.

[Hepatectomy for Intrahepatic Combined Hepatocellular Carcinoma Recurrence in a Hemophilia a Patient with Human Immunodeficiency Virus and Hepatitis C Virus-A Case Report].

A 40's Japanese man had a history of blood transfusion and administration of treatment coagulation factors for hemophilia A since he was 6 years old. He has been on IFN treatment for hepatitis C since he was 14 years old. Lastly, he has been undergoing HAART therapy for human immunodeficiency virus infection since he was 18 years old. Three years ago, he underwent partial hepatectomy for a tumor located in segment 8 of his liver and was diagnosed with combined hepatocellular carcinoma(CHC). Two years and 7 months after the operation, 2 intrahepatic recurrences were detected in the left lobe. He was referred to our hospital to undergo curative resection, and we performed a left lobectomy of the liver for the CHC recurrences. Perioperatively, supplemental factor Ⅷ was administered via APTT. Its activity was used as an index. Postoperatively, the patient was well, was discharged 13 days after surgery, and remained recurrence-free for 4 months.

[A Resected Case of Metachronous Solitary Metastasis of Jejunum after Surgery of Triple Colon Cancers].

A 68-year-old man underwent partial colectomy and double-barrel colostomy for an obstructive colon cancer of the splenic flexure at another hospital 10 years before. He was referred to us with an examination of anemia pointed out in human dock. Lower gastrointestinal endoscopy revealed the tumor occupied the remnant descending colon. We performed remnant left hemicolectomy and diagnosed as triple colon cancers. Six months after the initial operation, he was admitted to us with the chief complaints of abdominal fulness and vomit. Abdominal CT and radiologic enteroclysis after decompression used the ileus tube revealed complete stenosis at the small intestine. We performed surgery with a suspicion of obstruction of the small intestine. The tumor, 5 cm in diameter, occupied the jejunum was detected, and partial resection of the jejunum was performed. Histologically, the tumor was diagnosed as solitary metastasis of jejunum.

Prospective Multicenter Study on the Prognostic and Predictive Impact of Tumor Budding in Stage II Colon Cancer: Results From the SACURA Trial.

PURPOSE: The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899). PATIENTS AND METHODS: Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients' registration. RESULTS: Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively (P < .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum (P < .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION: Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer.

OBJECTIVE: Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC), a randomised phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS) and performed T x N subset analysis. METHODS: A total of 1518 patients with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days, four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days, five courses). RESULTS: The 5-year DFS rates of the S-1 and UFT/LV group were 70.2 % and 66.9 %, respectively (HR 0.88; 95% CI 0.74 to 1.06; p=0.177), and non-inferiority of DFS was reconfirmed with a median of 63.5-month follow-up. The similarity of OS was also confirmed (HR 0.92; 95% CI 0.72 to 1.17; p=0.488); 5-year OS rates of the S-1 and UFT/LV group were 86.0 % and 84.4 %, respectively. No significant interactions were identified between the major baseline characteristics and DFS of the S-1 and UFT/LV groups, except for histological type; S-1 was more favourable in patients with poorly differentiated adenocarcinoma. Patient outcomes were well separated by TNM-substages (IIIA/IIIB/IIIC). With the patients divided into 20 subsets by T and N factors, the DFS and OS rates of T3 and N1 subset, which accounted for 62 % of stage IIIB patients and 44 % of all studied subjects, were significantly better than those of the other subsets in stage IIIB and similar to those of stage IIIA. CONCLUSIONS: Adjuvant therapy of S-1 for stage III colon cancer was reconfirmed to be non-inferior in DFS to those of UFT/LV after long follow-up. No difference in OS was also demonstrated. T3N1 patients might be considered separately from other patients included in stage IIIB because of its favourable outcome. TRIAL REGISTRATION NUMBER: NCT00660894.

A randomised-controlled trial of 1-year adjuvant chemotherapy with oral tegafur-uracil versus surgery alone in stage II colon cancer: SACURA trial.

BACKGROUND: Efficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone for stage II colon cancer. METHODS: Patients were randomly assigned to the surgery-alone group or UFT group (UFT at 500-600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729. RESULTS: A total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/IIB/IIC, the distribution was 84%/13%/3%. The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75-1.10; p = 0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgery-alone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65-1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66-1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence. CONCLUSIONS: Superiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT. TRIAL REGISTRATION: ClinicalTrials. Gov. #NCT00392899.

[Radiofrequency Ablation for Colorectal Liver Metastases].

AIM: The significance of radiofrequency ablation(RFA)for colorectal liver metastases(CRLM)remains to be elucidated. Therefore, this retrospective study aimed to evaluate the therapeutic efficacy of RFA for local recurrence of CRLM. SUBJECTS: Between June 2005 and June 2017, we retrospectively examined 63 patients(137 nodules)with CRLM who underwent RFA. RESULTS: The local recurrence rate was 36.5%, and the median local recurrence free survival(LRFS)was 26.3 months. We compared treatment background between the 2 groups with(50 nodules)and without(87 nodules)local recurrence. In the multivariate analysis, tumor size of the ablated lesion and method for ablation(direct tumor puncture)were independent risk factors for local recurrence. Receiver operating characteristic curve for tumor size of the ablated lesion showed an optimal cutoff value for tumor size of 1.8 cm(AUC=0.734, 95%CI: 0.612-0.855, p<0.0001). CONCLUSIONS: RFA for effective control of local recurrence of CRLM might be suitable for selected patients with tumor size of ablated lesion ofC1.8 cm and no touch ablation method.

[A Resected Case of Hilar Cholangiocarcinoma Confirmed as Pathological Complete Response Following Neoadjuvant S-1 Monotherapy].

A 74-year-old man was admitted to a local hospital with liver dysfunction. Imaging modalities revealed bile duct stenosis at the bifurcation of the anterior and posterior trunk. Exfoliative cytology of the bile and brushing cytology of the bile duct both revealed Class Ⅴ, and biopsy from the stenotic bile duct showed well differentiated adenocarcinoma. We diagnosed the patient with hilar cholangiocarcinoma and performed extended right bisectionectomy and biliary reconstruction after percuta- neous transhepatic right portal vein embolization(PTPE). Preoperatively, he was administered S-1(80mg/body weight/day) orally for 19 days. Histopathological assessment of the resected specimen revealed hemosiderin-laden macrophages without viable cancer cells, confirmingpatholog ical complete response(pCR).

Primary closure of a spontaneous esophageal rupture under hand-assisted laparoscopy: a case report.

Spontaneous rupture of the esophagus, which is also known as Boerhaave's syndrome, is a rare life-threatening condition that requires urgent surgical management. The optimal treatment involves surgical repair of the esophageal defect, which is usually accomplished via laparotomy, thoracotomy, or both, and mediastinal debridement. Here, we report a case of spontaneous rupture of the esophagus that was treated with suturing repair and drain insertion using a hand-assisted laparoscopic approach.