Prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer undergoing neoadjuvant chemotherapy followed by gastrectomy.

PURPOSE: In Japan, gastrectomy with D2 lymph node dissection and postoperative adjuvant chemotherapy are the standard treatments for locally advanced gastric cancer. Neoadjuvant chemotherapy (NAC) is not affected by postgastrectomy syndromes or postoperative complications. This multicenter retrospective study investigated the prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer who underwent NAC followed by gastrectomy. METHODS: Consecutive patients (n = 221) with advanced gastric cancer who underwent NAC followed by curative surgery were enrolled in this study. Prognostic factors including postoperative adjuvant chemotherapy were investigated using univariate and multivariate analyses. RESULTS: A multivariate analysis revealed that pathological lymph node metastasis (ypN) status and postoperative adjuvant chemotherapy were independent prognostic factors for the overall and relapse-free survival. Forty-five patients (20.4%) did not receive postoperative adjuvant chemotherapy. There were no significant differences between patients with and without adjuvant chemotherapy for all factors, except age. The most common reason for not undergoing postoperative adjuvant chemotherapy was a poor condition (n = 23). CONCLUSIONS: ypN status and postoperative adjuvant chemotherapy were independent prognostic factors in gastric cancer patients who underwent NAC followed by curative gastrectomy. It is important to maintain the patient's condition during NAC and the perioperative period so that they can receive postoperative adjuvant chemotherapy.

[FOLFIRI plus RAM Therapy in Later Line of Unresectable Colorectal Cancer].

FOLFIRI plus ramucirumab(RAM)therapy has been reported to be effective and safe in the RAISE trial as second-line treatment for unresectable colorectal cancer. It is hypothesized that RAM may be effective in patients with PD treated with FOLFIRI plus bevacizumab(Bev)due to different mechanism of action from that of Bev, which is also an angiogenesis inhibitor. From January 2017 to December 2021, we conducted a retrospective study of 6 patients who had PD with 5-FU, oxaliplatin, irinotecan, or Bev as first or second-line treatment at our institution and who received FOLFIRI plus RAM in later line treatment. The 6 cases consisted of 3 patients in the third-line treatment, 1 patient in the fourth-line treatment, and 2 patients in the sixth-line treatment. The anti-tumor effect was PD in all cases in the third-line and fourth-line treatment, but the 2 patients of sixth-line treatment were controlled diseases.

[A Case Report-A Successful Case of Distal Pancreatectomy with En Bloc Celiac Axis Resection for Locally Advanced Pancreatic Cancer with an Aberrant Right Hepatic Artery].

In cases of pancreatic cancer with anatomical variations of the hepatic artery, it is important to evaluate the hemodynamics of each case for surgical indication. We report the case of a 68-year-old man with locally advanced pancreatic cancer and an aberrant right hepatic artery who underwent distal pancreatectomy with celiac axis resection(DP-CAR). He was admitted to our institute due to abdominal discomfort. A CT scan showed pancreatic cancer invading the common hepatic artery. He underwent chemoradiotherapy with a diagnosis of locally advanced pancreatic cancer. After the tumor downstaging, we performed DP-CAR, which included a gastroduodenal artery and a proper hepatic artery resection. Even though delayed gastric emptying was observed after the operation, he was discharged on postoperative day 36.

Long-term adjuvant therapy for high-risk gastrointestinal stromal tumors in the real world.

PURPOSE: Three years of adjuvant imatinib is the standard therapy for gastrointestinal stromal tumors (GISTs) with high-risk features. The prognostic effects of long-term adjuvant therapy are unknown. PATIENTS AND METHODS: The prospective registry study recruited 515 patients with high-risk GISTs between Dec. 2012 and Dec. 2015 were analyzed. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints include overall survival (OS) and safety. The study was designed to compare RFS after 3.5 years of 3-year adjuvant therapy (3.0 ± 0.5 years: 3-year group) with that of more than 3.5 years (median 5.2 years: longer group). RESULTS: Five-year RFS and 5-year OS were 68.2% (95% confidence interval [CI] 63.8-72.1) and 92.3% (95% CI 89.5-94.4), respectively. The recurrence rate during adjuvant was estimated to be 2.9/100 person-years (95% CI 2.0-4.1) and those after the end of adjuvant, which appeared similar irrespective of the adjuvant duration or reason to stop adjuvant, were estimated 12.0/100 person-years (95% CI 10.2-14.0). The 5-year RFS rates of 3-year and longer groups were 78.7% (95% CI 70.8-84.7) and 92.7% (95% CI 85.2-96.4), respectively. RFS after 3.5 years of the longer group was significantly better than that of the 3-year group (adjusted hazard ratio [HR] 0.56; 95% CI 0.39-0.78; P < 0.001). CONCLUSION: The recurrence risk of high-risk GISTs after adjuvant therapy is similar irrespective of the adjuvant duration and imatinib adjuvant may not cure but may delay recurrence. RFS after long-term adjuvant therapy appeared better than that after 3-year adjuvant.

New response evaluation criteria using early morphological change in imatinib treatment for patients with gastrointestinal stromal tumor.

BACKGROUND: The introduction of molecularly targeted drugs, including imatinib, has greatly improved the prognosis of gastrointestinal stromal tumor (GIST), and based on the different response image, the methods of response evaluation have been established for GISTs. Furthrmore, the best response evaluation using them has been reported to be associated with progression-free survival (PFS) in imatinib treatment. However, since it is more important to predict the clinical outcomes of imatinib treatment in "early treatment phase", new predicting factor in earlier stage is desired to work out the whole strategy of each patient. Early morphological change (EMC) was previously reported as a predictive marker for molecularly targeted drugs in metastatic colorectal cancer. The purpose of the present study was to verify the efficacy of EMC in predicting the outcome in patients with GIST receiving imatinib at early evaluation. METHODS: We retrospectively reviewed 66 patients. EMC in computed tomography (CT) image was evaluated, and the patients were categorized into two groups: active MR (morphological response) (+) group and active MR (-) group. We investigated the association between the presence of active MR and clinical outcomes. RESULTS: Forty-five patients had active MR ( +). The median progression-free survival (PFS) in patients with/without active MR was 49/23 months (P = 0.0039). CONCLUSION: The evaluation criteria based on EMC could be a sensitive method to predict the clinical outcome of imatinib treatment for patients with unresectable GIST.

Long-term outcomes of single-incision versus multiport laparoscopic colectomy for colon cancer: results of a propensity score-based analysis.

BACKGROUND: Long-term outcomes of single-incision laparoscopic colectomy (SILC) for colon cancer (CC), as practiced in real-world settings, especially in relation to disease stage, have not been established. We examined, retrospectively, both short- and long-term outcomes of SILC versus those of multiport laparoscopic colectomy (MPLC) performed for CC in a propensity-score-matched cohort. METHODS: The study involved 263 patient pairs matched 1:1 from among 691 patients who, between January 2008 and May 2014, underwent either SILC or MPLC for a primary solitary CC at our hospital. Short-term and long-term operative outcomes were compared between the two groups. RESULTS: Operation time was the only surgical outcome that varied significantly between the two groups (p = 0.0004). Overall 5-year cancer-specific survival (CSS) in the SILC group was 93.7 (95% CI 89.6-96.2)%, and CSS per pathological stage (I, II and III) was 98.5 (90.0-99.8)%, 96.0 (88.2-98.7)%, and 88.3 (79.6-93.6)%, respectively, whereas overall 5-year CSS in the MPLC group was 93.3 (89.4-95.9)%, and CSS per pathological stage was 100%, 95.4 (88.3-98.3)%, and 84.1 (74.1-90.8)% (p = 0.5278, 0.2679, 0.7666, and 0.9073), respectively. Overall 3-year disease-free survival (DFS) in the SILC group was 94.0 (90.2-96.4)%, and 3-year DFS per pathological stage was 98.6 (90.4-99.8)%, 90.1 (81.4-95.0)%, and 79.0 (69.4-86.2)%, respectively, whereas overall 3-year DFS in the MPLC group was 93.2 (89.4-95.7)%, and 3-year DFS per pathological disease stage was 100%, 94.5 (87.4-97.7)% and 75.5 (64.7-83.8)% (p = 0.2829, 0.7401, 0.4335 and 0.8518), respectively. Thus, oncological outcomes did not differ significantly between groups. Incisional hernia occurred in 21 (8.0%) SILC group patients and 17 (6.5%) MPLC group patients, without a significant between-group difference (p = 0.6139). CONCLUSION: Our data indicate that perioperative and oncological outcomes of SILC performed for CC are comparable to those of MPLC performed for CC.

Long-term outcomes of single-incision versus multiport laparoscopic totally extra-peritoneal inguinal hernia repair: a single-institution experience of 186 consecutive cases.

PURPOSE: This retrospective study was conducted to compare the long-term outcomes of single-incision totally extraperitoneal (S-TEP) inguinal hernia repair and conventional multiport totally extraperitoneal (M-TEP) inguinal hernia repair. METHODS: The study population included 186 consecutive patients (S-TEP, n = 149; M-TEP, n = 37) who underwent elective surgery for inguinal hernia at Osaka Police Hospital between 2011 and 2013. RESULTS: No significant between-group difference was found in patient or hernia characteristics or in perioperative outcomes, with the exception of age (S-TEP group vs. M-TEP group: median 69 [IQR 60-75] years vs. 64 [55-69] years, respectively; P = 0.019). Furthermore, no significant between-group difference was found in follow-up time (5.5 [3.0-5.8] vs. 5.4 [3.1-5.7] years, P = 0.839), recurrence rate (0.6 vs. 2.4%, P = 0.358), chronic pain (1.2 vs. 0%, P = 1.000), feeling the mesh (2.3 vs. 7.1%, P = 0.142), or movement limitation (0.6 vs. 0%, P = 1.000). All chronic symptoms were "mild but not bothersome." A metachronous contralateral inguinal hernia developed in 8.1% of patients. CONCLUSION: The long-term outcomes of S-TEP repair were comparable to those of M-TEP, with rates of recurrence, chronic pain, feeling the mesh, and movement limitation falling within acceptable limits.

[Effect of Endoscopic Resection on Prognosis in T1b Colorectal Cancer].

With the advancement of endoscopic resection(ER)of colorectal cancer, surgical resection after ER has been increasing. This study evaluated the effects of initial ER on short- and long-term outcomes in T1b colorectal cancer. This retrospective cohort study enrolled patients with pathological T1b colorectal cancer who underwent colorectal surgical resection between 2008 and 2018. A total of 239 eligible patients were divided into 2 groups: patients initially treated using surgical resection with lymph node dissection(LND)(surgery alone, n=142)and patients treated using initial ER and additional surgical resection with LND(surgery after ER, n=97). No significant differences were observed in short-term outcomes(ie, operative time, blood loss, or postoperative complications)or the long-term outcomes(ie, recurrence rate, overall survival rate, or recurrence free survival rate)between groups.

[A Case of Carcinomatous Meningitis from Gastric Cancer with Improvement of QOL by Ventriculoperitoneal Shunt].

In cases where carcinomatous meningitis leads to hydrocephalus and increases intracranial pressure, patients present with exacerbated pain and several neurological symptoms. It is reported that multidisciplinary therapy, including radiation therapy, drug therapy, and surgery, is performed for patients with carcinomatous meningitis; however, it is rarely successful. Ventriculoperitoneal shunting(V-P shunt)is a surgical intervention that might relieve the pain temporarily and improve the quality of life. VPS should be taken into consideration in line with patients' and their families' intentions since the overall survival is fairly short.

[Nodular Lymphocyte-Predominant Hodgkin Lymphoma(NLPHL)Which Originate from the Mesentery-A Series of Two Cases].

Nodular lymphocyte-predominant Hodgkin lymphoma(NLPHL)is a subtype of Hodgkin lymphoma. It is uncommon in Japan, and only a few cases of NLPHL originating from the mesentery have been reported. Most patients with NLPHL present in the early stage, but some patients have malignancy at initial presentation. We should perform staging laparotomy for the diagnosis and treatment of cases in which a lymph node biopsy is difficult.

[Case Series of the TAS-102 plus Bevacizumab(Bev)Combination Therapy in Unresectable Advanced Colorectal Cancer].

A phase-Ⅱtrial of TAS-102 plus bevacizumab(Bev)combination therapy showed a progression-free survival(PFS)of 3.7-4.6 months. Here, we report 12 cases of unresectable advanced recurrent colorectal cancer treated with TAS-102 plus Bev therapy at our hospital between June 2017 and February 2020. The median PFS was 6 months(2-12). Adverse events greater than Grade 3 were neutropenia(33.3%), febrile neutropenia(8.3%), thrombocytopenia(8.3%), and vomiting (8.3%). The frequency of non-hematotoxicity was low. In conclusion, the TAS-102 plus Bev therapy may be a useful option for the late-line treatment of unresectable advanced recurrent colorectal cancer.

[Launching Robot-Assisted Laparoscopic Surgery for Rectal Cancer in Our Hospital-Short-Term Results].

Robot-assisted laparoscopic surgery(RALS)for rectal cancer has been covered by National Health Insurance in Japan since April 2018. We launched RALS in our hospital in October 2019 and now report the short-term results(up to January 2020). Altogether, 15 consecutive patients(12 men, 3 women: median age 70 years)with rectal cancer underwent RALS during that period. For the first 2 cases, we performed RALS under the instruction of an experienced proctor from another institution. Among the 15 patients, 6 underwent high anterior resection and 9 low anterior resection. Median operating time was 358 min, median intraoperative blood loss was 0 mL, and there were no apparent intraoperative complications. Median postoperative length of hospital stay was 13 days, and only 1 patient developed a high-grade complication(Clavien-Dindo Grade Ⅲb)postoperatively. Hence, RALS for rectal cancer was launched successfully in our institution.

[A Case of Slow-Growing Intrahepatic Cholangiocarcinoma after Resection of Gastric Cancer].

An 83-year-old woman was given a diagnosis of gastric cancer and received distal gastrectomy 9 years ago. Three years later, CT revealed a tumor measuring 13 mm in diameter in hepatic segment 7. She was followed for 5 years, and the size of the tumor did not change. Eight years later after gastrectomy, the tumor size slightly enlarged to 17 mm, and biopsy revealed adenocarcinoma. The patient underwent liver resection of segment 7. The pathological diagnosis was well differentiated intrahepatic cholangiocarcinoma(ICC). No sign of recurrence has been found during a 1-year. This case, in which the patient was followed for 5 years before curative surgical treatment, is significant, because it demonstrates the slow-growing nature of ICC.

[A Case of Disseminated Carcinomatosis of the Bone Marrow Developing 15 Months after Gastrectomy].

The patient was a 60-year-old man who underwent distal gastrectomy for gastric cancer. The pathological diagnosis was Stage ⅡB. He received adjuvant chemotherapy(capecitabine plus oxaliplatin: CapeOX)for 6months and the postoperative course was uneventful. One year and 3 months after surgery, he visited the outpatient department for acute lower back pain. Blood tests showed elevated ALP(3,752 U/L), LDH(308 U/L), and CA19-9(69.4 U/mL)levels. Bone scintigraphy showed multiple bone metastases to the femora, ischium, iliac bone, vertebrae, sternum, costae, and scapulae in a super bone scan. The onset of disseminated intravascular coagulation(DIC)was observed later. The patient was diagnosed with disseminated carcinomatosis of the bone marrow. Radiation therapy was performed and anti-RANKL monoclonal antibody was administered for the bone metastases. Recombinant human soluble thrombomodulin was administered for DIC. He received chemotherapy( TS-1 plus cisplatin: SP)but died 4 months after the diagnosis. The prognosis of disseminated carcinomatosis of the bone marrow is extremely poor. We report this case along with a literature review.

[A Case of Complete Response to Lower Rectal Cancer after Preoperative Chemotherapy with CapeOX Therapy].

A 70 -year-old male patient was referred to our hospital with the chief complaint of hemafecia. Colonoscopy was performed and revealed bulky rectal cancer at 10 cm from the anal verge. After 4 courses of capecitabine plus oxaliplatin(Ca peOX)therapy as preoperative chemotherapy, colonoscopy and computed tomography(CT)revealed significant reduction of the tumor. We performed laparoscopic lower anterior resection and ileostomy. Histopathological examination revealed no residual tumor cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 1 year postoperatively.

[Eight Cases of Esophagus and Tracheobronchial Stenting for Advanced Esophageal Cancer].

Malignant stricture and fistula of the esophagus and tracheobronchus adversely affect the quality of life(QOL)in patients with advanced esophageal cancer. Stenting is one ofthe therapies available for these patients. We investigated the outcomes ofesophagus and tracheobronchial stenting in our institution. Eight patients with advanced esophageal cancer underwent double stenting from 2010 to 2016. Among them, 4 patients underwent double stenting as planned. One patient underwent an emergency tracheal stenting because ofstenosis ofthe trachea caused by esophageal stenting. Three patients underwent tracheobronchial stenting later on because ofan increase in the tumor size after esophageal stenting. Dysphagia score was improved in 5(67.5%)out ofthe 8 patients. Respiratory symptoms were improved in all patients, and 4 patients(50.0%) were discharged. The median survival time after esophageal stenting was 70.5 days. Esophagus and tracheobronchial stenting for advanced esophageal cancer was useful for the improvement of the QOL.

Downregulation of SIRT4 Expression Is Associated with Poor Prognosis in Esophageal Squamous Cell Carcinoma.

OBJECTIVE: SIRT4, a mitochondria-localized sirtuin, represses glutamine metabolism by inhibiting glutamate dehydrogenase (GDH). The current study aimed to evaluate the clinical and biological significance of SIRT4 in esophageal squamous cell carcinoma (ESCC). METHODS: The study comprised 172 patients with surgically resected ESCC in two independent cohorts. SIRT4 mRNA expression was analyzed in Cohort 1 (n = 79) and SIRT4 protein expression in Cohort 2 (n = 93). The association of SIRT4 expression with clinicopathological parameters and prognosis was assessed. Furthermore, the biological role of SIRT4 in ESCC cell lines was examined. RESULTS: SIRT4 expression was not correlated with any clinicopathological parameters in both cohorts. In Cohort 1, low-SIRT4-expression cases had poorer overall survival than high-SIRT4-expression cases (p = 0.016). In Cohort 2, SIRT4-negative cases had poorer overall survival and disease-free survival than SIRT4-positive cases (p = 0.011 and 0.0026). Multivariate analysis revealed that SIRT4 expression was an independent prognostic factor for overall survival (HR = 2.06, p = 0.038). The rate of distant recurrence was significantly higher in SIRT4-negative cases than in SIRT4-positive cases (39.4 vs. 7.4%; p = 0.0023). In vitro, SIRT4 knockdown significantly increased GDH activity and promoted cell proliferation and migration. CONCLUSION: SIRT4 is a potential prognostic biomarker in ESCC.

[A Case of Esophageal Cancer Complicated with Idiopathic Thrombocytopenic Purpura].

The patient was a 58-year-old woman. She was diagnosed with idiopathic thrombocytopenic purpura (ITP) when she was 41 years old. Splenectomy was performed at age 55; however, there was no response (NR). Therapy with prednisolone was continued. She underwent endoscopic examination because of dysphagia, and an esophageal tumor was revealed. She was diagnosed with esophageal squamous cell carcinoma (Mt, cT3N1M0, Stage ⅢA). She received high-dose g-globulin therapy and platelet transfusion before surgery, and the platelet count subsequently increased to 11.0×10(4) mm3. A subtotal esophagectomy was performed. The platelet count was low immediately after surgery; however, it increased after POD5. The patient was discharged without complications. She is alive without recurrence 9 years after surgery. This is the first report of esophageal cancer complicated with ITP that was not responsive to splenectomy. We report this case along with a discussion.

A novel locally operated master-slave robot system for single-incision laparoscopic surgery.

PURPOSE: Single-incision laparoscopic surgery (SILS) provides more cosmetic benefits than conventional laparoscopic surgery but presents operational difficulties. To overcome this technical problem, we have developed a locally operated master-slave robot system that provides operability and a visual field similar to conventional laparoscopic surgery. MATERIAL AND METHODS: A surgeon grasps the master device with the left hand, which is placed above the abdominal wall, and holds a normal instrument with the right hand. A laparoscope, a slave robot, and the right-sided instrument are inserted through one incision. The slave robot is bent in the body cavity and its length, pose, and tip angle are changed by manipulating the master device; thus the surgeon has almost the same operability as with normal laparoscopic surgery. To evaluate our proposed system, we conducted a basic task and an ex vivo experiment. RESULTS: In basic task experiments, the average object-passing task time was 9.50 sec (SILS cross), 22.25 sec (SILS parallel), and 7.23 sec (proposed SILS). The average number of instrument collisions was 3.67 (SILS cross), 14 (SILS parallel), and 0.33 (proposed SILS). In the ex vivo experiment, we confirmed the applicability of our system for single-port laparoscopic cholecystectomy. CONCLUSION: We demonstrated that our proposed robot system is useful for single-incision laparoscopic surgery.

[A case of salvage surgery for gastric wall recurrence of esophageal cancer after chemoradiotherapy].

The patient was a 69-year-old man. He underwent chemoradiotherapy for advanced esophageal cancer, and achieved a complete response. However, 16 months after chemoradiotherapy, lymph nodes metastases were detected along the celiac artery. He underwent chemotherapy followed by radiotherapy. Positron emission tomography (PET)-computed tomography (CT) at 3 months after radiotherapy showed new uptake of fluorodeoxyglucose (FDG) at the cardiac region of the stomach. Endoscopy revealed a tumor that was diagnosed as squamous cell carcinoma by biopsy. Under the diagnosis of gastric intramural recurrence of esophageal cancer, he was referred to our hospital. Proximal gastrectomy and resection of lymph nodes along the celiac artery were performed. The patient is alive without recurrence 1 year after surgery. Metachronous gastric intramural recurrence of esophageal cancer is very rare. We report this case with a review of the literature.