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Treatment policy: Esophagus/Stomach

Treatment indicators for esophageal cancer

Overview:

The Japan Esophageal Society published its Guidelines for Diagnosis and Treatment of Esophageal Cancer (third revision) in April 2012. Our department has created even more specific treatment indicators, based on these guidelines, and implements treatment based on this.
At present, we use upper gastroenterological endoscopy, ultrasound endoscopy, multi-slice CT scanning and FDG-PET, to provide a more accurate diagnosis of the extent of advancement of the cancer, and determine treatment policy depending on the following conditions, but in some cases concomitant conditions and comorbidities, etc., may result in a change in policy.

Treatment Policies

Cases in which the invasion depth of the primary tumor is limited to the mucosal layer (T1a) and no lymph node metastasis is observed

Endoscopic submucosal dissection (ESD) is the primary choice. If the ESD sample is determined in pathology to be either m1 (mucosal epithelium) or m2 (submucous coat), a wait-and-see approach is adopted. If it has reached m3 (muscular layer of mucosa), a wait-and-see approach is taken if vascular invasion cannot be confirmed. If vascular invasion is confirmed, thorascopic esophageal resection and lymph node removal are implemented.

Cases in which the invasion depth of the primary tumor reaches the submucosal layer (T1b) and no lymph node metastasis is observed

Thorascopic esophageal resection and lymph node removal are implemented. If lymph node metastasis is confirmed in post-surgical pathology, additional post-surgical chemotherapy is administered.

Cases in which the invasion depth of the primary tumor reaches the muscle layer (T2) or the outer membrane (T3), or lymph node metastasis is observed (Stage II and III).

Anti-cancer drug treatment administered before surgery, after which esophageal resection implemented and three-region lymph nodes removed.

Cases in which the primary tumor has exceeded the outer membrane, and infiltrated other organs (windpipe and aorta)

Chemoradiotherapy implemented. In cases where significant tumor shrinkage is confirmed and curative resection is considered possible, surgery may be carried out.

Cases in which distal metastasis is confirmed (metastasis to lungs, liver, bones, etc.)

Anti-cancer drug treatment carried out. Depending on the condition, additional radiotherapy may be administered, stents inserted, and enterostomy or gastrostomy implemented. Cases not responding to conventional treatments are treated as part of the clinical trial into peptide vaccine therapy.

Additional explanation of treatment details

Thorascopic Esophageal Rsection

Since 2009, we have been implementing fully prone thorascopic esophageal resections. With the patient in the prone position, trocars are inserted in five locations in the right thoracic region, and the procedure is carried out under carbon dioxide pneumothorax.
This has many advantages in comparison to conventional thoracotomy (minimal thoracotomy procedure); there is little pain involved, the patient can return to moving around quickly, and there is little reduction in respiratory function post-surgery. This contributes to a reduction in complications. We are currently using this procedure in cases of esophageal cancer up to those with outer membrane infiltration, with no pleural ankylosis. It is not used, however, in cases with large upper thoracic neoplasm, and cases subsequent to chemoradiotherapy.

The patient is prone. The surgeon and the assistant watch the same monitor while implementing the procedure.

Chemotherapy (Anti-Cancer Drugs)

Conventionally, standard chemotherapy for esophageal cancer involves combined administration of cisplatin and 5-FU, but recently, the triple DCF therapy, which involves the combined additional use of docetaxel with the above. Problematically, however, the side effects of DCF are relatively strong. We are engaged in a clinical trial of separated DCF combined therapy, in which the component drugs are administered separately with the aim of reducing these side effects. This method has been clearly shown to be more effective than FP therapy (in shrinking tumors), and to have comparatively mild side effects, except for bone-marrow suppression. The current method has been applied to Stage II and III pre-surgical chemotherapy treatment, and is achieving excellent results.

Chemoradiotherapy

Our department offers chemoradiotherapy, in cooperation with the radiology department. Radiotherapy is carried out using 3D irradiation, with the combined administration of cisplatin and 5-FU. The radiation dose is changed as appropriate for the objective, but in cases requiring curative radiation, in principle the dose is a minimum of 50 Gy.

Perioperative Management

Since esophageal cancer surgery is the most complex procedure carried out within the field of gastroenterological surgery, it is considered to be frequently accompanied by complications. For this reason, at this hospital, we engage in various measures throughout the perioperative period, in cooperation with other departments in the Hospital, to prevent post-surgical complications. One example of this is the perioperative rehabilitation program. With the full cooperation of our rehabilitation department, we have created a perioperative rehabilitation program specially suited to esophageal cancer surgery, which begins prior to surgery and includes training to strengthen the heart and lungs, muscle training, respiratory physical therapy, post-surgery seated position retention, walking training (from the day after surgery), all of which are implemented from the day after surgery until the patient leaves hospital, facilitating the patient being able to return to moving around as normal at an early stage. We are also engaged in swallowing rehabilitation, in order to counter swallowing difficulties subsequent to esophageal cancer surgery. Additionally, our work is backed up by a range of different departments, in areas including intensive care (ICU), oral care (Oral Surgery), post-surgery pain management (Anesthesiology), cardiac function assessment and treatment (Cardiology, Pulmonary Medicine, Pulmonary Surgery), head and neck function screening and evaluation (Otolaryngology), etc., facilitating an integrated approach to esophageal medicine.
As a result of this, in the 193 cases handled during the five years between 2007 and 2011, the rate of post-surgical respiratory complications was 4.1%, suture failure occurred in 4.1%, anastomotic stenosis occurred in 2%, and (permanent) recurrent neural paralysis occurred in 1%, all of which are low in comparison to national averages.

Treatment Indicators for Gastric Cancer

Overview

Pre-surgery, the location of the cancer, its size, histological type, invasion depth, and whether or not metastasis has occurred are accurately diagnosed, and treatment is implemented in line with the state of advancement. Based on the “Guidelines for Treatment of Gastric Cancer” published by the Japanese Gastric Cancer Association, we have created further, more developed, independent guidelines for the treatment of gastric cancer, and base our selection of treatment on these. We select treatment methods for patients with concomitant conditions and comorbidities based on a balance between the extent of advancement and their whole-body condition.

Early Stage Gastric Cancer

Treatment methods determined in accordance with the diagram.

Advanced Gastric Cancer

Treatment methods determined in accordance with the diagram.

Ⅰ.  Cases where curative resection is possible

  1. Radical surgery: resection of minimum of 2/3 of stomach + D2 removal
  2. Non-radical surgery
      Extended surgery: Combined resection of other organs and D3 removal, etc., alongside resection of minimum of 2/3 of stomach

1.  Radical surgery

<U  Area)>

  • Fundectomy: Differentiated N0 cases where lesions are limited to the U area, with invasion depth to T2
  • Complete removal: Cases other than the above

< M and L Areas>

  • Distal gastrectomy: Adoral discission is closer to the anus than the cardia, and no metastasis is demonstrated in lymph nodes No. 1, 2, 4sa, 10 or 11
  • Complete removal: Cases other than the above

2. Extended Surgery

  • Scope of gastric resection determined based on radical surgery
  • Joint resection of other organs, removal of lymph nodes D2 and above

< Joint resection of other organs>

  1. Application
    In principle, where infiltration is confirmed in organs that can be jointly resectioned, joint resection may be proactively implemented in cases where a level B cure may be anticipated. Since this is a highly invasive procedure, there are cases in which it cannot be carried out due to pre-surgical complications.
  2. Joint resection
    1. Spleen removal: Upper advanced gastric cancer
        Cases in which metastasis to lymph node No. 4sa has been clearly demonstrated
         Cases in which removal of lymph node No. 10 is necessary
      *In cases where metastasis to lymph node No. 10 has been confirmed, pre-surgery chemotherapy may be implemented.
    2. Transverse colon resection
    3. Pancreatic tail resection, pancreatic body and tail resection
    4. Joint resection of other organs (liver, adrenal gland, diaphragm, etc.)

< Para-aortic lymph node removal>

  1. Cases in which metastasis is demonstrated to the para-aortic lymph node, and there are no other non-curative factors
    *Ordinarily, where metastasis is demonstrated to the para-aortic lymph node prior to surgery, pre-surgery chemotherapy is implemented.
    *Since this is a highly invasive procedure, there are cases in which it cannot be carried out due to pre-surgical complications.

  2. Scope of removal
    Scope of removal of para-aortic lymph node (No. 16)
    16a2 inter, latero, 16b1 inter, latero

3. Screening Laparoscopy

  1. Application
    Gastric cancers in which pre-surgical diagnosis gives cause to suspect serosal membrane infiltration, or large type 3 and 4 gastric cancers
  2. Objective
  3. Search for peritoneal dissemination, peritoneal washing cytology

 

4.  Selection of Surgical method in cases of gastric cancer that has infiltrated the esophagus

  • Cases where esophageal infiltration distance is 3 cm or less
    : transperitoneal diaphragm incision approach
  • Cases where esophageal infiltration distance is more than 3 cm
    : thoracotomy approach - left thoracotomy (between seventh or sixth ribs)

*Pre-surgical chemotherapy may be implemented in cases in which metastasis to lower mediastinal lymph nodes is confirmed prior to surgery.

 

5. Reconstructive Surgery

  1. Distal gastrectomy
    Billroth I or Roux-en Y methods
  2. Complete gastric removal
    R-Y method
  3. Fundectomy
    In principle, jejunal interposition surgery, with esophagus-stomach joining where remaining stomach is sufficiently large

6. Pre-surgery Chemotherapy (Neoadjuvant Chemotherapy)

  1. Objective
    a)  Down staging
    b) Control of micrometastasis in areas not reached by surgery
    c) Organ preservation
    Based on the above, objectives are an improvement in curative resection rates and improved prognosis
  2. Application (may be conducted as part of a clinical trial)
    a) Cases testing positive in peritoneal washing cytology
    b) Cases of large type 3 and 4 gastric cancers
    c) Cases in which pre-surgery imaging diagnosis leads to a suspicion of bulky N2, or metastasis to the para-aortic or group 3 lymph nodes
    d) T4b cases, with infiltration of major blood vessels (celiac artery, common hepatic artery, etc.) or the pancreatic head, or infiltration of organs that cannot be jointly resected

7. Post-surgery additional chemotherapy (Adjuvant chemotherapy)

  1. Objectives:
    The objective is control of recurrence, thereby improving prognosis.
  2. Application:
    Cases defined as pStageII and II by the 14th edition of Gastric Cancer Treatment Regulations (excluding pT1 and T3 (SS) / N0 cases)
  3. Anti-cancer drugs
    S-1 (administered for 1 year post-surgery)

Ⅱ. Cases in which curative resection is not possible

  1. Metastasis to liver
    1. Single metastasis
      Cases in which primary tumor can also be curatively removed by extended surgery: gastric resection + liver resection        Other than the above: chemotherapy (+ palliative resection)
    2. Multiple metastasis
      Chemotherapy (+ palliative surgery)
      Palliative surgery is carried out in order to improve imminent symptoms such as bleeding and stenosis caused by the primary tumor.
  2.  Metastasis to peritoneal membranes
    1. Cases with no clear peritoneal membrane nodes, but which test positive in (washing) cytology only
      Pre-surgery chemotherapy. Subsequently, cases demonstrating a negative result in a second screening laparoscopy are treated with extended surgery, followed by post-surgery chemotherapy.
    2. Cases demonstrating clear peritoneal membrane nodes
      Chemotherapy
  3. Widespread lymph node metastasis (Bulky N3 and remote lymph node metastasis)
    • Chemotherapy, followed by curative surgery if tumor shrinkage is noted
    • Palliative surgery

III. Clinical research: Bridging research and clinical practice

Patients who give their agreement are asked to participate proactively in clinical trials towards the development of better treatment methods and diagnostic methods, etc., and are also offered the opportunity to participate in some of the largest-scale clinical trials in Japan, such as those run by the Japan Clinical Oncology Group (JCOG) etc.